leptin and Pre-Eclampsia

Endothelial dysfunction is a major risk factor for many cardiovascular diseases, notably hypertension. Obesity increases the risk of endothelial dysfunction in association with increasing production of the adipokine leptin. Preclinical studies have begun to unravel the mechanisms whereby leptin leads to the development of endothelial dysfunction, which are sex-specific. This review will summarize recent findings of mechanisms of leptin-induced endothelial impairment in both male and females and in pregnancy.. Leptin receptors are found in high concentrations in the central nervous system (CNS), via which leptin promotes appetite suppression and upregulates sympathetic nervous system activation. However, leptin receptors are expressed in many other tissues, including the vascular endothelial cells and smooth muscle cells. Recent studies in mice with vascular endothelial or smooth muscle-specific knockdown demonstrate that endothelial leptin receptor activation plays a protective role against endothelial dysfunction in male animals, but not necessarily in females. Clinical studies indicate that women may be more sensitive to obesity-associated vascular endothelial dysfunction. Emerging preclinical data indicates that leptin and progesterone increase aldosterone production and endothelial mineralocorticoid receptor activation, respectively. Furthermore, decades of clinical studies indicate that leptin levels increase in the hypertensive pregnancy disorder preeclampsia, which is characterized by systemic endothelial dysfunction. Leptin infusion in mice induces the clinical characteristics of preeclampsia, including endothelial dysfunction.. Novel preclinical data indicate that the mechanisms whereby leptin promotes endothelial dysfunction are sex-specific. Leptin-induced endothelial dysfunction may also play a role in hypertensive pregnancy as well.

Topics: Animals; Endothelial Cells; Female; Humans; Hypertension; Leptin; Male; Mice; Obesity; Pre-Eclampsia; Receptors, Leptin

Resistin, a diminutive secretory adipokine, has been linked to obesity and its related ailments. A growing body of evidence suggests that resistin may also be related to the pathogenesis preeclampsia. However, results of previous studies were not consistent. We performed a systematic review and meta-analysis to evaluate the level of circulating resistin in women with PE. A systematic search of Medline, Web of Science, and Embase databases from inception to April 28, 2023, was conducted to identify studies that compared blood resistin levels in pregnant women with and without PE. A random-effects model was utilized to pool the results, accounting for heterogeneity. The present study analyzed eighteen datasets from sixteen observational studies. The results of the meta-analysis demonstrated a statistically significant increase in blood resistin levels among women with PE compared to the control group. (standardized mean difference=0.35, 95% confidence interval: 0.16 to 0.54, p<0.001; I2=74%). The findings of the subgroup analysis indicate that various study characteristics, including study design, timing, and methods for measuring resistin, matching of body mass index between cases and controls, and study quality scores did not exert a significant impact on the outcomes. Nonetheless, it is noteworthy that the diagnostic criteria for PE employed in the studies included in the analysis may have influenced the results (p for subgroup difference=0.001). Women with preeclampsia exhibit a greater concentration of resistin in circulation when compared to healthy pregnant controls.

Topics: Adipokines; Adiponectin; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Resistin

Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic compensatory mechanisms involving leptin during pregnancy play a decisive role in the development of pre-eclampsia (PE) and give rise to compromised intrauterine growth conditions and aberrant birth weight of offspring. This review was compiled to elucidate the metabolic background of PE and its relationship with adverse intrauterine growth conditions through the examination of leptin as well as to describe possible mechanisms linking leptin to fetal growth restriction. This review illustrates that leptin in PE is dysregulated in maternal, fetal, and placental compartments. There is no single set of unifying mechanisms within the spectrum of PE, and regulatory mechanisms involving leptin are specific to each situation. We conclude that dysregulated leptin is involved in fetal growth at many levels through complex interactions with parallel pregnancy systems and probably throughout the entirety of pregnancy.

Topics: Animals; Female; Fetal Growth Retardation; Humans; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Leptin

An understanding of the origin of cancer is critical for cancer prevention and treatment. Complex biological mechanisms promote carcinogenesis, and there is increasing evidence that pregnancy-related exposures influence foetal growth cell division and organ functioning and may have a long-lasting impact on health and disease susceptibility in the mothers and offspring. Nulliparity is an established risk factor for breast, ovarian, endometrial and possibly pancreatic cancer, whilst the risk of kidney cancer is elevated in parous compared with nulliparous women. For breast, endometrial and ovarian cancer, each pregnancy provides an additional risk reduction. The associations of parity with thyroid and colorectal cancers are uncertain. The timing of reproductive events is also recognized to be important. Older age at first birth is associated with an increased risk of breast cancer, and older age at last birth is associated with a reduced risk of endometrial cancer. The risks of breast and endometrial cancers increase with younger age at menarche and older age at menopause. The mechanisms, and hormone profiles, that underlie alterations in maternal cancer risk are not fully understood and may differ by malignancy. Linking health registries and pooling of data in the Nordic countries have provided opportunities to conduct epidemiologic research of pregnancy exposures and subsequent cancer. We review the maternal risk of several malignancies, including those with a well-known hormonal aetiology and those with less established relationships. The tendency for women to have fewer pregnancies and at later ages, together with the age-dependent increase in the incidence of most malignancies, is expected to affect the incidence of pregnancy-associated cancer.

Topics: Age Factors; Chorionic Gonadotropin; Epigenesis, Genetic; Estrogen Replacement Therapy; Estrogens; Female; Humans; Leptin; Menarche; Menopause; Neoplasms; Parity; Pre-Eclampsia; Pregnancy; Progesterone; Risk Assessment; Somatomedins

Preeclampsia is a syndrome occurring only in pregnancy characterized by systemic maternal inflammation and associated with the presence of the placenta. How these 2 aspects of the disease are linked has been the subject of numerous theories and ideas. Recently, there has been increasing interest in DNA shed from the placenta into the maternal circulation as a potential agent initiating the inflammatory response. This review will discuss the current evidence and future directions for placental DNA as the linking factor in preeclampsia in the context of other hypotheses.

Topics: Cell-Derived Microparticles; Cytokines; DNA; Female; Humans; Hypoxia; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Systemic Inflammatory Response Syndrome; Trophoblasts; Vascular Endothelial Growth Factor Receptor-1

Proteins secreted from adipocytes - so-called adipokines - influence metabolic and vascular function. Recent data suggest that various adipokines are dysregulated in gestational diabetes mellitus (GDM) and pre-eclampsia (PE) and might be of pathophysiological and prognostic significance in these complications of pregnancy. This review gives an overview on the regulation and pathophysiology of leptin and adiponectin in GDM and PE. Furthermore, data on novel adipokines including resistin, visfatin, retinol-binding protein 4 and vaspin are summarized.

Topics: Adiponectin; Diabetes, Gestational; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy

Pre-eclampsia is a unique disorder of human pregnancy with a great impact on maternal and perinatal morbidity and mortality worldwide and especially in developing countries. The aetiology is still unknown and the pathophysiology of the disease is the subject of extensive investigation. Recently, much of the interest of the investigators for the prediction of pre-eclampsia has been aimed at measurable manifestations of abnormal placentation, endothelial dysfunction and feto-maternal unit perfusion. Biomarkers constitute a novel approach to an early detection of the disease. Low maternal serum levels of PAPP-A and PP13 early in pregnancy are predictive for emerging pre-eclampsia. On the other hand, increased levels of homocysteine, ADMA, sEng, leptin and sFlt-1 in the 1st trimester, signal the onset of the disease later in pregnancy. After the onset of pre-eclampsia, increased serum levels of PAPP-A, ADMA, homocysteine and sFlt-1 are associated with the severity of the disease. The identification of biomarkers which can contribute to the early detection of pre-eclampsia is essential. It could then be possible to apply better surveillance and treatment protocols in such patients.

Topics: Antigens, CD; Arginine; Biomarkers; Endoglin; Female; Galectins; Homocysteine; Humans; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Receptors, Cell Surface; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

Leptin is a protein hormone synthesized and secreted by adipose tissue and also probably in other organs and systems in human body. It has multiple functions such as to regulate feed intake and energy balance, gonadal regulation, action in the hypothalamo-pituitary-gonadal axis, regulates the metabolism of the fetal-placental unit in the pregnancy, fertility and reproductive systems, actions in the endometrium, mammary gland with corresponding influences on important physiologic processes such as menstruation, pregnancy and lactation. In the gynecologic surgery the serum leptin concentration is also modified. The knowledge of serum leptin concentration in the oncological diseases is going-up. Leptin is modified in the choriocarcinoma, Meigs' syndrome and other tumors. A better understanding of regulatory mechanisms will have direct clinical significance, as leptin has been proposed to impact on those causes of human perinatal morbidity and mortality that are associated with abnormalities of fetal maturity and development, general concept growth, trophoblast endocrinology, and placental sufficiency. Further investigations in this area will be necessary to improve new knowledge and a better understanding of the actions about this hormone.

Topics: Energy Metabolism; Female; Fertility; Fetal Diseases; Fetal Organ Maturity; Genital Diseases, Female; Humans; Hydatidiform Mole; Hypothalamo-Hypophyseal System; Leptin; Meigs Syndrome; Placenta; Polycystic Ovary Syndrome; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Receptors, Leptin; Reproduction; Uterine Neoplasms

Topics: Activins; Biomarkers; Female; Humans; Inhibin-beta Subunits; Inhibins; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Diagnosis; Sensitivity and Specificity

Preeclampsia and intrauterine growth restriction are both characterized by placental malfunction. The pathological processes of abnormal trophoblast invasion, partial absence of maternal spiral artery modification, increased apoptosis of trophoblast cells, and placental ischemia are all associated with the release of specific molecules. These proteins, as well as cell-free fetal DNA and RNA might be detected in the maternal peripheral circulation, quantified, and used for early identification and prediction of preeclampsia and intrauterine growth restriction, prior to the appearance of the clinical symptoms. As preeclampsia and intrauterine growth restriction are associated with increased maternal, perinatal, and neonatal morbidity and mortality, early identification of these pregnancy associated complications will permit the design of appropriate preventive measures. In this review a variety of factors reported to be useful as potential markers for early detection of pregnancies at increased risk will be discussed. Molecules associated with the establishment of the placenta and essential in fetal-maternal interactions, like interleukin 2-receptor, insulinlike growth factor-1, and insulinlike growth factor binding protein-1, placenta growth factor, hepatocyte growth factor, inhibin A, activin A, and human chorionic gonadotrophin seem to be the most likely candidates for presymptomatic markers for preeclampsia and/or intrauterine growth restriction. Detection and discrimination of these molecules through the placental RNA in maternal plasma based strategy has become a realistic option.

Topics: ATPases Associated with Diverse Cellular Activities; Biomarkers; Cell Adhesion Molecules; Cytokines; Female; Fetal Growth Retardation; Fibronectins; Humans; Leptin; Metalloendopeptidases; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Pregnancy Proteins

Leptin is a 16-kDa polypeptide, encoded in humans by the LEP gene. This protein is probably involved in the regulation of ovarian function, oocyte maturation and embryo development, and in the implantation process. During pregnancy, leptin is produced in the placenta; its values increase in the maternal blood particularly in the second trimester and decline postpartum. Leptin levels may be abnormally high in pregnancies complicated by conditions such as diabetes mellitus and pre-eclampsia. The role of leptin in fetal physiology has not been clarified, although cord blood values correlate significantly with birth weight. It is expected that further research will provide new insight into the physiological importance of leptin in the pregnant woman and fetus.

Topics: Embryo Implantation; Female; Fetal Blood; Humans; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics

Pre-eclampsia, or pregnancy-induced hypertension, is a major cause of maternal and fetal morbidity and mortality complicating 7-10% of pregnancies. Although mechanisms underlying pre-eclampsia are not well understood, endothelial dysfunction is considered to underscore many of the pre-eclamptic manifestations including hypertension, proteinuria and edema. Leptin, the obese gene product from adipocytes, is produced by the placenta during pregnancy. Serum leptin levels are elevated under normal pregnancy especially during the second trimester, which rapidly decreases and returns to normal after delivery, indicating the role of leptin as a gestational hormone for energy balance. Recent studies have revealed that the placental production of leptin may be pathologically augmented under pre-eclampsia although conflicting data also have been reported. Nevertheless, hyperleptinemia and possible further augmentation under pre-eclampsia may predispose to the development of maternal leptin resistance, which may be a component of insulin resistance predisposing the onset of endothelial dysfunction. This review summarizes recent findings regarding the putative changes of serum leptin levels during pre-eclampsia and the potential consequences on the vascular system.

Topics: Animals; Drug Resistance; Endothelium, Vascular; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Reference Values

Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05). We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg. Resistin is a novel adipocyte-derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.

Topics: Adult; Animals; Eating; Female; Fetal Weight; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Maternal-Fetal Exchange; Mice; Mice, Transgenic; Nerve Growth Factor; Placenta; Placental Insufficiency; Pre-Eclampsia; Pregnancy; Pregnancy, Animal; Proteins; Resistin

Leptin, the protein encoded by the Ob gene in the adipose cell, is produced by the placenta during pregnancy. This review describes recent findings regarding the putative functions of leptin during pregnancy.. and methods. We searched the literature consulting Medline database.. Placental leptin production makes a substantial contribution to maternal circulating levels during pregnancy. Leptin has been detected in fetal plasma as early as week 18 of gestation, and umbilical leptin concentrations are closely related to birth weight. This has led to the hypothesis that fetal fat mass mainly determines fetal circulating leptin. Placental leptin production is increased in choriocarcinoma, preeclampsia and type 1 diabetes. Estrogens, hypoxia and insulin have been suggested as positive regulators of placental leptin production.. Maternal leptinemia might act as a sensor of energy balance during pregnancy. The presence of both leptin and leptin receptors in the placenta suggests that leptin can act by autocrine or endocrine pathways in the human placenta. The roles of fetal leptin and consequences of increased placental leptin production in pathological pregnancies have yet to be elucidated.

Topics: Birth Weight; Choriocarcinoma; Diabetes Mellitus, Type 1; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leptin; MEDLINE; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Umbilical Cord

Leptin, a hormone produced by adipose tissue and the placenta, is enhanced in the maternal circulation throughout pregnancy in both the human and the baboon ( Papio sp.), a proven nonhuman primate model for the study of human pregnancy. The presence of both leptin and its receptor in the fetus implies a role for the polypeptide as a regulator of in utero development, although localization in the placental trophoblast may relate to autocrine and/or paracrine regulatory functions in this important endocrine tissue. Although regulatory mechanisms remain incompletely defined, it has been suggested that cross talk occurs between the fetus, placenta, and maternal adipose stores. Placental estrogen, which is present in increasing concentrations with advancing gestation, is suggested to influence leptin synthesis in a tissue- and cell type-specific fashion. In this capacity, cellular hypoxia, diabetes, and preeclampsia are conditions that appear to be intimately linked to leptin dynamics. A better understanding of regulatory mechanisms will have direct clinical significance, as leptin has been proposed to impact on those causes of human perinatal morbidity and mortality that are associated with anomalies of fetal maturity and development, general conceptus growth, trophoblast endocrinology, and placental sufficiency.

Topics: Animals; Cell Hypoxia; Diabetes, Gestational; Embryonic and Fetal Development; Estrogens; Female; Gene Expression; Humans; Leptin; Papio; Pre-Eclampsia; Pregnancy; Receptors, Cell Surface; Receptors, Leptin; Trophoblasts

Preeclampsia, a common complications of pregnancy, is associated with an increase in the concentration of leptin in the maternal blood, which precedes the clinical onset of the disease. This review addresses the potential sources of leptin and considers the possible consequences, although at present these are entirely conjectural. The placenta is likely to contribute to the rise in leptin, and placental hypoxia and inflammatory mediators may be important stimuli. The possible protective and damaging sequelae of an increase in the maternal leptin concentrations may range from beneficial stimulation of fetal growth to an increase in blood pressure through stimulation of sympathetic activity. Further research is needed to determine if the rise in leptin plays a role in preeclampsia or whether it is a secondary and unrelated bystander.

Topics: Embryonic and Fetal Development; Female; Fetal Blood; Humans; Insulin Resistance; Leptin; Placenta; Pre-Eclampsia; Pregnancy

There is clear evidence of placental leptin production, as shown recently in trophoblast cultures and by dual in vitro placenta perfusion (median production of 225 pg/min per g of tissue; 98.4% released into the maternal and 1.6% into the fetal circulation). However, the physiological impact for the mother and the fetus is unclear. The classical role of leptin is to provide information about energy stores to the central nervous system, and to reduce appetite if the energy stores are full. In pregnancy, maternal plasma leptin concentrations are elevated, and lack the well established correlation with body fat energy stores that is observed in non-pregnant women, indicating an alternative function for leptin during pregnancy and fetal development. Maternal and fetal plasma leptin levels are dysregulated in pathological conditions such as gestational diabetes, pre-eclampsia and intra-uterine growth retardation, representing an effect or a cause of disturbances in the feto/placento/maternal unit.

Topics: Female; Fetal Blood; Fetal Growth Retardation; Fetus; Humans; Hypoxia; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications

Adipokines are predominantly secretory protein hormones from adipose tissue but may also originate in placenta and other organs. Cross-sectionally, we monitored maternal plasma concentration of adiponectin, resistin, and leptin and their mRNA expression in abdominal subcutaneous adipose tissue and placenta from preeclamptic (PE; n = 15) and healthy pregnant (HP; n = 23) women undergoing caesarean section. The study groups were similar in age and BMI, whereas HOMA-IR tended to be higher in the PE group. In fasting plasma samples, the PE group had higher concentrations of adiponectin (18.3 +/- 2.2 vs. 12.2 +/- 1.1 microg/ml, P = 0.011), resistin (5.68 +/- 0.41 vs. 4.65 +/- 0.32 ng/ml, P = 0.028), and leptin (34.4 +/- 3.2 vs. 22.7 +/- 2.1 ng/ml, P = 0.003) compared with the HP group. Adiponectin and leptin concentrations were still different between PE and HP after controlling for BMI and HOMA-IR, whereas resistin concentrations differed only after controlling for BMI but not HOMA-IR. We found similar mean mRNA levels of adiponectin, resistin, and leptin in abdominal subcutaneous adipose tissue in PE and HP women. When data were pooled from PE and HP women, resistin mRNA levels in adipose tissue also correlated with HOMA-IR (r = 0.470, P = 0.012) after controlling for BMI and pregnancy duration. Resistin mRNA levels in placenta were not significantly different between PE and HP, whereas leptin mRNA levels were higher in PE placenta compared with HP. Thus increased plasma concentrations of adiponectin and resistin in preeclampsia may not relate to altered expression levels in adipose tissue and placenta, whereas both plasma and placenta mRNA levels of leptin are increased in preeclampsia.

Topics: Adiponectin; Adipose Tissue; Adult; Female; Humans; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Resistin; Tissue Distribution

We have previously reported a reduced incidence of preeclampsia in women who were at risk and were taking vitamin C (1000 mg/d) and vitamin E (400 IU/d) supplements. In this study, we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preeclampsia.. Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously.. Indices of oxidative stress and placental function were abnormal in the placebo group. When the placebo group was compared with the women who were at low risk, ascorbic acid, plasminogen activator inhibitor-2, and placenta growth factor concentrations were decreased; and 8-epi-prostaglandin F(2alpha),leptin, and the plasminogen activator inhibitor-1/-2 ratio were increased. In the group that received vitamin supplements, ascorbic acid, 8-epi-prostaglandin F(2alpha), leptin, and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk.. Antioxidant supplementation in women who were at risk of preeclampsia was associated with improvement in biochemical indices of the disease.

Topics: Adult; Ascorbic Acid; Dietary Supplements; Endometrium; Female; Humans; Leptin; Oxidative Stress; Placenta; Placenta Growth Factor; Placental Insufficiency; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Risk; Vitamin E

Hyperleptinemia may be part of the insulin resistance syndrome. We studied serum leptin in preeclampsia, which is an insulin-resistant state, and sought associations between leptin and insulin or insulin sensitivity during and after pregnancy. Twenty-two proteinuric preeclamptic women and 16 normotensive controls were studied during the third trimester. Leptin was higher in preeclampsia (mean +/- SE, 34.6 +/- 3.9 v 20.0 +/- 3.3 microg/L, P = .002) and correlated directly with the level of proteinuria (r = .47, P = .03) and normal pregnancy (r = .52, P = .04), whereas insulin sensitivity as assessed by an intravenous glucose tolerance test showed no relationship to leptin. Leptin was 19.0 +/- 3.6 microg/L in 14 preeclamptic women and 10.1 +/- 2.0 microg/L (P = .11) in 11 controls 3 months after delivery. Leptin correlated directly with insulin both in preeclamptic puerperal women (r = .63, P = .02) and in controls (r = .81, P = .003). Leptin and insulin sensitivity correlated only in preeclamptic puerperal women (r = -.59, P = .02). In conclusion, (1) serum leptin is elevated in preeclampsia, (2) insulin is an important determinant of serum leptin in preeclamptic and normotensive women both during pregnancy and in the puerperium, and (3) hyperleptinemia may be part of the insulin resistance syndrome also in women with prior preeclampsia.

Topics: Adult; Body Mass Index; Female; Humans; Insulin; Insulin Resistance; Leptin; Pre-Eclampsia; Pregnancy; Radioimmunoassay; Reference Values

Leptin (LP) and neuropeptide Y (NPY) are involved in the regulation of appetite and energy expenditure. As was shown in our previous studies healthy non pregnant and pregnant women are characterized by a significant positive correlation between maternal body mass index (BMI) and plasma leptin concentration. On the other side participation of both leptin and obesity in the pathogenesis of essential hypertension is presumed. The present study aimed to answer the following question: to what extend LP and NPY are involved in the pathogenesis of arterial hypertension in pregnant women with EPH gestosis. One to 2 days before delivery plasma LP and NPY concentration were estimated in 43 healthy pregnant women, in 18 pregnant women with EPH gestosis and in 26 healthy non pregnant women. In pregnant women with EPH gestosis, mean arterial blood pressure (MAP) (114.6 +/- 1.3 mm Hg) and mean leptinaemia (21.9 +/- 8.5 ng/ml) were significantly higher than in healthy pregnant women (89.1 +/- 0.9 mm Hg and 15.0 +/- 1.3 ng/ml respectively) and in non pregnant women (MAP--91.56 +/- 1.4 mm HG i LP--10.9 +/- 1.7 ng/ml). In healthy pregnant women, in women with EPH gestosis and in healthy nonpregnant women plasma NPY concentrations were of similar magnitude (42.3 +/- 4.1 vs 43.7 +/- 8.5 vs 50.7 +/- 6.1 pg/ml respectively). In pregnant women with EPH gestosis a significant positive correlation was found between diastolic blood pressure or MAP and plasma NPY concentration. Leptinaemia was significantly correlated with systolic, diastolic and MAP respectively only when results obtained in both groups of pregnant women were analyzed together.. 1) leptin seems to be involved in the regulation of blood pressure both in healthy and preeclamptic pregnant women, 2) participation of NPY in the pathogenesis of hypertension in preeclamptic women is likely.

Topics: Adult; Blood Pressure; Body Mass Index; Female; Humans; Leptin; Neuropeptide Y; Pre-Eclampsia; Pregnancy

The aim of this study was to compare maternal blood and umbilical-cord leptin, spexin and visfatin levels during delivery in severe preeclampsia (PE) with controls, and to evaluate whether any clinical or demographic variables had independent associations with them.. This is a case-controlled observational study consisting of 45 pregnant women with severe PE and a control group consisting of gestational age-matched 45 healthy pregnant women. We examined the leptin, spexin, and visfatin levels in serum samples taken from maternal blood and umbilical cords during cesarean section in both groups. Leptin, spexin, and visfatin levels were measured by enzyme-linked immunosorbent assay.. The maternal leptin and visfatin levels were significantly higher and the maternal spexin levels were significantly lower in the PE group than in the control group (p < 0.001). Similar to the maternal adipokine levels, the umbilical-cord leptin and visfatin levels were significantly higher and the spexin levels were significantly lower in the PE group (p < 0.001). We found a significant positive correlation between maternal body mass index and maternal blood and umbilical-cord serum leptin and visfatin levels in both groups (p < 0.001).. The leptin, spexin and visfatin levels were significantly altered in the nondiabetic preeclamptic women in our study. We believe that the main reason for these changes may be the hypoxic placenta to protect the fetus and maintain its nutrition.

Topics: Adipokines; Case-Control Studies; Cesarean Section; Female; Humans; Leptin; Nicotinamide Phosphoribosyltransferase; Pre-Eclampsia; Pregnancy; Pregnant Women

Topics: Animals; Female; Humans; Infant; Inhibitor of Differentiation Protein 2; Insulin; Insulin, Regular, Human; Leptin; Male; Mice; Obesity; Placenta; Pre-Eclampsia; Pregnancy; Trophoblasts

The ratio between circulating levels of leptin and soluble leptin receptor (sOB-R), the free leptin index (FLI), is used as a marker of leptin resistance. Therefore, the aim of our study was to investigate the FLI in mild pre-eclamptic pregnancies in a nested case-control study within a prospective observational study. Circulating levels of leptin and sOB-R levels rise significantly during pregnancy in healthy (p < 0.05) (n = 46) and pre-eclamptic pregnancies (p < 0.05) (n = 20). Serum levels of leptin were significantly higher in pre-eclamptic compared to healthy pregnancies at second and third trimesters of pregnancy (p < 0.05). Additionally, serum levels of sOB-R were significantly lower in pre-eclamptic pregnancies during the second and third trimesters of pregnancy compared to healthy pregnancies (p < 0.05). Moreover, we found that FLI did not vary significantly during pregnancy in healthy women (p > 0.05), while it increases in pre-eclamptic pregnancies (p < 0.05). Indeed, FLI was significantly higher at second and third trimesters of pregnancy in pre-eclamptic compared to healthy pregnancies (p < 0.05). In addition, FLI was significantly higher in the luteal phase compared with the follicular phase of the menstrual cycle in eumenorrheic women (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed the ability of leptin (AUC = 0.72) and FLI (AUC = 0.67) as a reliable predictor for mild pre-eclampsia during the second trimester of pregnancy. In conclusion, our findings show that FLI were significantly increased in mild pre-eclamptic pregnancies and allowed us to hypothesize that this rise might alter leptin bioavailability and bioactivity which might lead to the sympathetic hyperactivity and the hypertensive disorders during pregnancy.

Topics: Case-Control Studies; Female; Humans; Leptin; Longitudinal Studies; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Receptors, Leptin

Pregnancy - induced hypertension (PIH), preeclampsia (PE), and gestational diabetes (GDM) are common adverse outcomes in pregnancy.. To find out whether preconceptual leptin levels differ in subsequent pregnancy between control vs. GDM and hypertensive pregnancy groups.. Data was from The Cardiovascular Risk in Young Finns Study and The Medical Birth Register of Finland. Of 293 subjects 71 developed GDM, 27 PIH/PE and 201 were controls.. Leptin was higher in GDM (p < 0.0001) and PIH/PE (p = 0.0002) groups compared to control. GDM group was robust to BMI matching (p = 0,0081).

Topics: Diabetes, Gestational; Female; Finland; Humans; Hypertension, Pregnancy-Induced; Leptin; Pre-Eclampsia; Pregnancy

Patients with preeclampsia demonstrate increases in placental leptin production in midgestation, and an associated increase in late gestation plasma leptin levels. The consequences of mid-late gestation increases in leptin production in pregnancy is unknown. Our previous work indicates that leptin infusion induces endothelial dysfunction in nonpregnant female mice via leptin-mediated aldosterone production and endothelial mineralocorticoid receptor (ECMR) activation, which is ablated by ECMR deletion. Therefore, we hypothesized that leptin infusion in mid-gestation of pregnancy induces endothelial dysfunction and hypertension, hallmarks of clinical preeclampsia, which are prevented by ECMR deletion.. Leptin was infused via miniosmotic pump (0.9 mg/kg per day) into timed-pregnant ECMR-intact (WT) and littermate-mice with ECMR deletion (KO) on gestation day (GD)11-18.. Leptin infusion decreased fetal weight and placental efficiency in WT mice compared with WT+vehicle. Radiotelemetry recording demonstrated that blood pressure increased in leptin-infused WT mice during infusion. Leptin infusion reduced endothelial-dependent relaxation responses to acetylcholine (ACh) in both resistance (second-order mesenteric) and conduit (aorta) vessels in WT pregnant mice. Leptin infusion increased placental ET-1 (endothelin-1) production evidenced by increased PPET-1 (preproendothelin-1) and ECE-1 (endothelin-converting enzyme-1) expressions in WT mice. Adrenal aldosterone synthase (. Collectively, these data indicate that leptin infusion in midgestation induces endothelial dysfunction, hypertension, and fetal growth restriction in pregnant mice, which is ablated by ECMR deletion.

Topics: Animals; Blood Pressure; Endothelin-1; Female; Humans; Hypertension; Leptin; Mice; Mice, Knockout; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Mineralocorticoid

To measure and compare serum levels of leptin and lipid profile parameters in primigravida women with PE and normotensive primigravida.. Analytical cross-sectional study.. Department of Physiology and Cell Biology, University of Health Sciences, Lahore, from 2018 to 2020.. Preeclamptic (PE, group A) and normal primigravida (PG, group B) with gestational age 30-36 weeks were recruited from tertiary care hospitals. After written and informed consent, blood samples were taken. Serum was separated and stored at -80oC until processed. CBC and lipid profile of each patient was also done using automated lab machines. Serum levels of leptin were calculated by ELISA. The data was entered and analysed in SPSS version 20.. The mean serum levels of leptin (ng/ml) in PE (group A) were significantly raised compared to normotensive PG (group B) at 33.44±12.91 and 4±6.20 respectively (p.

Topics: Cross-Sectional Studies; Female; Humans; Hyperlipidemias; Infant; Leptin; Lipids; Pre-Eclampsia

Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be identified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. We evaluate the performance of oxidative stress-associated potential biomarkers for FGR and PE, and their relationship with clinical characteristics.. A prospective clinical pilot study was performed in healthy controls and women with pregnancies complicated by severe FGR with or without PE. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Placentas were examined microscopically. Descriptive statistics and receiver operating characteristics statistics were performed.. Mothers with both severe FGR and PE had significantly reduced FT levels (p < 0.001) and PlGF levels (p < 0.001), and increased levels of plasma IMA (p < 0.05), sFlt (p < 0.001), leptin (p < 0.05) and sRAGE (p < 0.01) compared to women with FGR only. Systemic FT levels were significantly inversely associated with blood pressure (p < 0.01) and plasma IMA (p < 0.001), leptin (p = 0.01) and sRAGE (p < 0.001). Systemic FT and leptin showed significant discriminative ability to differentiate mothers with both FGR and PE from mothers with uncomplicated pregnancies or pregnancies complicated by FGR only.. There is a significant discriminative capacity of FT, IMA, leptin and sRAGE that harbor potential as biomarkers of pregnancies complicated by combined FGR and PE.

Topics: Adult; Biomarkers; Female; Fetal Growth Retardation; Humans; Inflammation; Leptin; Oxidative Stress; Pilot Projects; Placenta; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Prospective Studies; Receptor for Advanced Glycation End Products; Serum Albumin, Human; Sulfhydryl Compounds; Vascular Endothelial Growth Factor Receptor-1

This study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation.. Retrospective discovery and longitudinal confirmation.. Maternity units from two US hospitals.. Six previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation.. Biomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays.. Our discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks' gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation.. Our study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test.

Topics: Biomarkers; Ceramides; Female; Humans; Leptin; Placenta; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Retrospective Studies

To evaluate a level of expression of endoglin (Eng), leptin (Lep), placental growth factor (PlGF), and hypoxia-inducible factor-1alpha (HIF-1α) in placenta among women with pre-eclampsia and diabetes mellitus (DM), considering the method of glycemia correction and preconception care.. A retrospective cohort study was conducted. A total of 124 women were divided into following groups: type 1 DM (. The highest level of placental expression of Eng was observed in the PE group (20.34%). The same trend was also typical for T1DM (not planned) and insulin-treated groups: T2DM and GDM. An amount of cell with an PlGF expression was significantly higher in the control group (12.2%), while the lowest was observed in the pre-eclampsia group (1.18%) and T1DM (not planned) (1.26%). The placental leptin expression within each DM group was increased among the patients with unplanned pregnancy and those who received insulin therapy. We observed the lowest Lep expression in the PE group (6.3%). High level of HIF-1α expression was detected in T1DM (not planned) (30.44%) and PE (29.64%) as compared to the control group (11.62%). In T2DM and GDM insulin groups, the HIF-1α expression was significantly higher as compared to diet groups.. The obtained data show that DM and pre-eclampsia are associated with changes in angiogenic and metabolic placental factor expressions. The degree of changes depends on preconception care and the control of glycemia level during pregnancy.

Topics: Adult; Diabetes, Gestational; Endoglin; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leptin; Placenta; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Retrospective Studies

[Figure: see text].

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensins; Benzimidazoles; Biphenyl Compounds; Female; Humans; Leptin; Leucyl Aminopeptidase; Placenta; Pre-Eclampsia; Pregnancy; Renin-Angiotensin System; Tetrazoles; Uterine Artery; Vascular Resistance

The pathogenesis of pre-eclampsia (PE) is associated with significant maternal and neonatal complications, an increased inflammatory response, placental hypoxia, and endothelial dysfunction, coupled with differential exosomal release profiles with immune modulation effects. Hence, this study evaluated the impact of circulating exosomes derived from early and late-onset pre-eclamptic pregnancies on inflammatory cytokine secretion by BeWo cells.. Exosomes were isolated from plasma obtained from early-onset pre-eclamptic (EOPE; n = 15), late-onset pre-eclamptic (LOPE; n = 15), and gestational age-matched normotensive pregnancies (N ≤ 33 weeks; n = 15 and N ≥ 34 weeks; n = 15). Human BeWo cells were treated with characterized and quantified exosomes (100 μg/mL exosomal protein per pregnant group) for 24 h. The immunoassay method was used to measure the concentration of IL-8, IL-10, leptin, and HIF-α.. Exosome administration from women with EOPE and LOPE increased IL-8 and decreased IL-10 expression in BeWo cells.. Cumulatively, our data demonstrated that circulating exosomes from the placenta and activated immune cells potentially influence inflammatory cytokine production in pre-eclamptic pregnancies.

Topics: Adult; Cell Line, Tumor; Culture Media, Conditioned; Exosomes; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-10; Interleukin-8; Leptin; Pre-Eclampsia; Pregnancy; Young Adult

We examined whether maternal serum cytokine profiles of mothers with early-onset fetal growth restriction (FGR) were associated with delivery within 2 weeks after sampling during the third trimester.. This exploratory prospective cross-sectional study included a total of 20 singleton fetuses with early-onset FGR and 31 healthy controls. Maternal serum samples during the early third trimester were analyzed for 23 cytokines.. Of 20 fetuses with early-onset FGR, 14 had delivery within 2 weeks after sampling. Multivariate analysis revealed that maternal serum concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble CD40 ligand (sCD40L) were independently associated with delivery within 2 weeks in early-onset FGR. Among cases of early-onset FGR, concentrations of almost all maternal serum cytokines were similar. Maternal serum sVEGFR-1 concentrations were high when delivery occurred within 2 weeks. Maternal serum sCD40L concentrations were elicited only in cases in which delivery within 2 weeks occurred due to fetal deterioration.. We identified two biomarkers, one specific for FGR and the other dependent on severity, that were significant components of angiogenic activities and inflammation factors. Imbalances in serum protein expression may have a substantial effect on the pathogenesis of FGR.

Topics: Adult; Biomarkers; Birth Weight; Case-Control Studies; CD40 Ligand; Cesarean Section; Cross-Sectional Studies; Cytokines; Elective Surgical Procedures; Endoglin; Female; Fetal Growth Retardation; Heparin-binding EGF-like Growth Factor; Humans; Infant, Newborn; Infant, Small for Gestational Age; Labor, Induced; Leptin; Male; Multivariate Analysis; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Premature Birth; Time Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats. Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 μg/kg/day of leptin (LEP), or 120 μg/kg/day of leptin+30 μg/kg/day of resibufogenin (L + RBG) or 30 μg/kg/day of resibufogenin (RBG) from Day 1-20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum. SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups. The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat.

Topics: Animals; Blood Pressure; Bufanolides; Endothelin-1; Endothelium, Vascular; Female; Intercellular Adhesion Molecule-1; Leptin; Pre-Eclampsia; Pregnancy; Proteinuria; Rats; Rats, Sprague-Dawley; Vascular Cell Adhesion Molecule-1

Dysregulated RNA editing is well documented in several diseases, such as cancer and neurodegenerative diseases. The extent to which RNA editing might be involved in diseases originated in the placenta remains unknown. Here, we have systematically profiled RNA editome on the placentae, 9 from patients with early-onset severe preeclampsia (EOSPE) and 32 from normal subjects, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The RNA editing events at 2 microRNA binding sites in 3'-untranslated region of the

Topics: Adult; Binding Sites; Cell Line; Female; Gene Expression Profiling; Gene Expression Regulation; Gestational Age; Humans; Leptin; MicroRNAs; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimesters; RNA Editing; Severity of Illness Index; Up-Regulation

Preeclampsia (PE) is a serious complication of pregnancy, the pathogenesis of which is largely unknown. We hypothesize that adipocytokines may play a role in the pathogenesis of PE, particularly in obese women, and evaluate leptin and adiponectin as potential first trimester markers for predicting PE.. A cohort of 2503 pregnancies, containing 93 PE pregnancies, was divided into women with normal weight, moderate, or severe obesity. All pregnancies had serum adiponectin and leptin measured in first trimester. Logistic regression was used to model PE with maternal characteristics and concentrations of the biomarkers.. In obese women a lower concentration of adiponectin was found in PE pregnancies; the concentration was lowest in the severely obese (p = 0.005). No association was found in normal weight women (p = 0.72). Leptin concentration had no association with PE in normal weight and moderately obese (p = 0.175-0.072), however in women with severe obesity a lower level of leptin was found (p = 0.049). The AUC was 0.73 for the ROC curve of combined maternal characteristics and adiponectin. Using adiponectin in women with moderate to severe obesity the sensitivity was 72.9% and the specificity was 49%.. In severely obese women, PE is associated with low serum adiponectin and leptin concentrations in first trimester. This indicates that the inability of adipokine regulation to adapt to severe obesity may play a role in the pathogenesis of PE. Adipocytokines may contribute in identification of risk pregnancies among severe obese.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Leptin; Logistic Models; Obesity; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Risk Assessment; Young Adult

Involvement of leptin in the pathogensis of preeclampsia (PE) is still a controversy subject.\ Several researches reported the changes in serum leptin in high altitude (HA) residents. The aim\ of the present work was to investigate the impact of oxidative stress (OS) induced by HA residence\ on maternal serum leptin in PE and if there was a significant correlation between the serum leptin\ with either OS or endothelial inflammatory markers. One hundred fifty eight pregnant women were\ included in this study, divided into: low altitude normal pregnancies (NL), HA normal pregnancies\ (NH), low altitude preeclamptic (PL), and HA preeclamptic (PH) who presented to the obstetrics and\ gynecology outpatient clinic in both Muhayl (500 m over sea level) and Abha General Hospitals (all\ of them resident at Alsoda district with the average altitude 2700 m over sea level). Serum leptin,\ superoxide dismutase (SOD) activity, malondialdehyde (MDA), plasma nitrite/nitrate (NOx), serum\ tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), blood urea nitrogen (BUN) and creatinine\ were determined. Both NH and PL groups showed significant increases in leptin (P < 0.01), SOD (P <\ 0.01), MDA (P < 0.001), NOx (P < 0.001), TNF-α (P < 0.001) and IL-6 (P < 0.001) compared with the\ NL group without any significant changes between both groups. The PH group showed significant\ accentuation of the previously measured parameters (P < 0.001 for all) compared with all other\ groups (NL, NH and PL groups). We can conclude that the combination of PE and HA residence\ resulted in significantly elevated maternal serum leptin suggesting involvement of leptin in the\ pathogenesis of PE accentuated by HA residence.

Topics: Altitude; Female; Humans; Leptin; Oxidative Stress; Pre-Eclampsia; Pregnancy

The mechanism underlying the pathogenesis of preeclampsia (PE) has been previously investigated but remains to be elucidated. Among numerous biomarkers that are associated with the pathogenesis of PE, leptin is most frequently investigated. Although studies concerning the association between PE and the expression of leptin in the serum and placenta have been conducted, the results are conflicting and inconsistent. Furthermore, the expression of leptin and its receptors in the placental bed and their association with PE, to the best of our knowledge, has not been previously reported. Therefore, to determine the association between the expression of leptin and its receptor, and pathogenesis and onset period of PE, placental bed tissues were obtained from cesarean section deliveries. The mRNA and protein expression levels of leptin and its receptor were investigated in normal pregnancies (n=18), pregnancies complicated with early‑onset PE (n=9) and late‑onset PE (n=9) by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that the mRNA and protein expression of leptin in the placental bed was significantly increased in the PE groups compared with normal controls and was associated with the onset period of PE. Furthermore, as evidenced by immunostaining, leptin was upregulated in endothelial cells of the placental bed in the PE groups, with a particularly strong upregulation in activated endothelial cells from patients with early‑onset PE. The results of the present study indicate that altered expression of leptin in the placental bed may contribute to the pathogenesis of PE.

Topics: Adult; Biomarkers; Blood Pressure; Female; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Leptin

Hypertensive disorders, fetal growth restriction and preterm birth are major obstetrical complications and are related to impaired placentation. Early identification of impaired placentation can advance clinical care by preventing or postpone adverse pregnancy outcome.. Determine whether sonographic assessed placental vascular development and concomitant changes in inflammation- and/or angiogenesis-related serumproteins differ in the first trimester between uncomplicated pregnancies and pregnancies with adverse outcome.. This prospective longitudinal study defines adverse pregnancy outcome as conditions associated with impaired placentation; fetal growth restriction, hypertensive disorder, preterm birth and placental abruption. The vascularization index, flow index, vascularization flow index and placental volume were determined at 8, 10 and 12 weeks pregnancy from 64 women using 3D power Doppler. Serum levels were analyzed for Angiopoetin-1 and -2, Leptin, VEGF-R, VEGF, and EGF.. The vascularization index and vascular flow index increased in uneventful pregnancies with almost 50% between 8 and 12 weeks, resulting in a ∼50% higher vascularization index at 12 weeks compared to women with an adverse pregnancy outcome. Women with an adverse pregnancy outcome (n = 13) had significantly lower indices and placental volumes at all time points measured and these indices did not increase between 8 and 12 weeks. Reduced vascular development was associated with increased Angiopoietin-1 levels at 8 and 12 weeks and increased Leptin levels at 8 weeks.. Pregnancies with an adverse outcome caused by conditions associated with impaired placentation differ from uneventful pregnancies in having reduced placental vascularization accompanied by elevated circulating levels of Angiopoietin-1 and Leptin already in the first trimester.

Topics: Adult; Angiopoietin-1; Female; Humans; Leptin; Longitudinal Studies; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Prospective Studies; Ultrasonography, Prenatal; Vascular Endothelial Growth Factor A

The objective of the study was to analyse leptin, IGF-1, Apo A, lipoproteins, haem oxygenase-1 (HO-1) in maternal sera and venous umbilical cord sera of newborn babies of 25 preeclamptics (group II), and 25 normotensive pregnant women (group I) as markers of obesity and growth in preeclamptic and normotensive pregnant women. Apo A I and II levels were estimated by competitive immunoassay using direct chemiluminiscence technology. Haem oxygenase-1 (HO-1), leptin and IGF-1 were analysed by ELISA. Maternal and cord blood levels of homocysteine, folic acid, lipid profile (namely, total cholesterol, triglycerides, LDL-C, VLDL-C and HDL-C), Haem oxygenase 1 were higher in preeclamptic women as compared to normotensive pregnant women. Serum and cord blood Apo A-I and Apo B, leptin levels, IGF-I were lower in preeclamptic women as compared to normotensive pregnant. The findings of high serum HO-1 levels in maternal and cord blood in preeclampsia supports the role of oxidative stress and excessive inflammatory response in the pathogenesis of preeclampsia. It seems likely that IGF-1 and leptin play a central role in controlling foetal growth. There is increasing evidence that the foundations of life-long health are, in part, laid in the uterus. Findings of present study suggest that alterations in biochemical markers of growth and obesity occur in mothers and foetuses and modifications of uterine environment can be of help to prevent future cardiovascular risk. Impact statement Preeclampsia has been reported to be associated with an increased risk of later life cardiovascular disease. However, information regarding how obesity increases the risk of preeclampsia is limited. Atherogenic milieu occurring during pregnancy persists into adulthood and foetal growth retardation is strongly associated with adult atherosclerosis. There is conflicting evidence regarding alterations of IGFs in preeclamptic pregnancies and deficit in circulating and cord blood IGF-1 levels in intrauterine growth restricted newborns and a correlation between IGF-1 levels and birth weight have been reported. Leptin is a predictor of cardiovascular risk independent of insulin resistance. Emerging evidence supports an important role for the haem oxygenase system (HO-1) in the maintenance of a healthy pregnancy, especially during pathological challenge. Conflicting data are available regarding HO-1, leptin and IGF -1 in preeclamptic mothers. The extent to which they mediate foetal growth and develo

Topics: Apolipoprotein A-I; Biomarkers; Case-Control Studies; Female; Fetal Blood; Heme Oxygenase-1; Humans; Insulin-Like Growth Factor I; Leptin; Pre-Eclampsia; Pregnancy

Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified.. PP13 was measured in first trimester (week 10+3-13+6) maternal serum from 120 PE pregnancies and 267 control pregnancies and was correlated with clinical parameters. The population screening performance of PP13 in combination with the PE markers pregnancy associated plasma protein A (PAPPA) and free leptin index (fLI) was assessed by Monte Carlo simulation.. In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8-85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1-50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4-142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI.. PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

Topics: Adolescent; Adult; Biomarkers; Female; Galectins; Humans; Leptin; Middle Aged; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Young Adult

The incidence of pre-eclampsia, a multisystem disorder of pregnancy, is fourfold higher in type 1 diabetic than non-diabetic women; it is also increased in women with features of the metabolic syndrome and insulin resistance. In a prospective study of pregnant women with type 1 diabetes, we measured plasma levels of adipokines known to be associated with insulin resistance: leptin, fatty acid binding protein 4 (FABP4), adiponectin (total and high molecular weight [HMW]; also known as high molecular mass), retinol binding protein 4 (RBP4) and resistin and evaluated associations with the subsequent development of pre-eclampsia.. From an established prospective cohort of pregnant type 1 diabetic women, we studied 23 who developed pre-eclampsia and 24 who remained normotensive; for reference values we included 19 healthy non-diabetic normotensive pregnant women. Plasma adipokines were measured (by ELISA) in stored samples from three study visits (Visit 1- Visit 3) at different gestational ages (mean ± SD): Visit 1, 12.4 ± 1.8 weeks; Visit 2, 21.7 ± 1.4 weeks; and Visit 3, 31.4 ± 1.5 weeks. All the women were free of microalbuminuria and hypertension at enrolment. All study visits preceded the clinical onset of pre-eclampsia.. In all groups, leptin, the ratio of leptin to total or HMW adiponectin, FABP4 concentration, ratio of FABP4 to total or HMW adiponectin and resistin level increased, while total and HMW adiponectin decreased, with gestational age. At Visit 1: (1) in diabetic women with vs without subsequent pre-eclampsia, leptin, ratio of leptin to total or HMW adiponectin, and ratio of FABP4 to total or HMW adiponectin, were increased (p < 0.05), while total adiponectin was decreased (p < 0.05); and (2) in normotensive diabetic vs non-diabetic women, total adiponectin was elevated (p < 0.05). At Visits 2 and 3: (1) the primary findings in the two diabetic groups persisted, and FABP4 also increased in women with subsequent pre-eclampsia (p < 0.05); and (2) there were no differences between the two normotensive groups. By logistic regression analyses after covariate adjustment (HbA. As early as the first trimester in type 1 diabetic women, adipokine profiles that suggest insulin resistance are associated with subsequent pre-eclampsia, possibly reflecting maternal characteristics that precede pregnancy. These associations persist in the second and third trimesters, and are independent of BMI. Insulin resistance may predispose women with type 1 diabetes to pre-eclampsia.

Topics: Adipokines; Adiponectin; Adult; Diabetes Mellitus, Type 1; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Prospective Studies; Resistin; Retinol-Binding Proteins, Plasma; Young Adult

Leptin, primarily produced by adipocytes, is implicated in the development of pre-eclampsia. This study examines placental leptin production and serum leptin levels in HIV infected and uninfected normotensive and pre-eclamptic pregnancies. Placental leptin production was analysed by RT-PCR and serum leptin levels by ELISA in normotensive (n = 90) and pre-eclamptic (n = 90) pregnancies which were further stratified by HIV status. Placental leptin production was higher in pre-eclampsia compared to normotensive pregnancies irrespective of HIV status (p = .04). Serum leptin was non-significantly raised in HIV uninfected (p = .42) but lower in HIV-infected (p = .03) pre-eclampsia. The latter had lower BMI (p = .007) and triceps skin-fold thickness (p < .001) than the HIV uninfected groups with a significant correlation between serum leptin and triceps skin-fold thickness (p < .001), indicative of less adipose tissue in HIV-infected women with consequently lower serum leptin. Thus, serum leptin levels are not indicative of increased placental production when pre-eclampsia is associated with HIV infection.

Topics: Adult; Case-Control Studies; Female; HIV Infections; Humans; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; RNA, Messenger

It is theorized that adipokines play a critical role in the pathophysiology of preeclampsia, particularly with their pro-inflammatory and inflammatory features.. To investigate serum leptin levels in pregnancies complicated with preeclampsia and severe preeclampsia.. Maternal serum leptin levels were analyzed by solid phase enzyme amplified sensitivity immunoassay (EASIA) method in 23 patients with mild preeclampsia, 29 patients with severe preeclampsia, and 28 healthy pregnant controls.. Mean serum leptin levels did not differ statistically between patients with mild preeclampsia, severe preeclampsia, and the controls (10.77 ng/ml, 13.40 ng/ml, and 8.43 ng/ml, respectively). Also, there was no relationship between serum leptin levels and the gestational ages of the participants.. Serum leptin levels are not associated with preeclampsia. Leptin measurements are not affected with the gestational age. The role of leptin in the pathophysiology of preeclampsia should be evaluated cautiously.

Topics: Adult; Biomarkers; Female; Gestational Age; Humans; Leptin; Pre-Eclampsia; Pregnancy; Severity of Illness Index; Young Adult

Alterations in serum adipokines in preeclampsia remain vague. We investigated the roles of leptin, adiponectin and resistin and their relationships with clinical characteristics in normotensive and preeclamptic patients.. A case-control study was carried out in a cohort of 74 preeclampsia(PE) and 79 healthy pregnant women. Serum levels of leptin, adiponectin and resistin were measured by enzyme-linked immunosorbent assay.. The mean body mass index(BMI), the serum leptin and resistin levels were significantly higher in the PE group than in the control group (p<0.001). The resistin/creatinine ratio was also higher in the PE group than in the control group (p=0.018). No significant difference was observed in the serum adiponectin level between both groups. Serum leptin levels were positively correlated with BMI (r=0.301, p<0.001) and negatively correlated with newborn birth weight (r=-0.435, p<0.001). Serum resistin levels were also negatively correlated with birth weight (r=-0.229, p=0.005) but were unrelated to BMI. Logistic regression showed that BMI≥28 and serum leptin levels were independent factors of PE. Leptin was a potential mediator between BMI and PE (p<0.001), and the mediating effect accounted for 22.54% of the total effect.. Leptin, resistin, and obesity play important roles in the onset of PE. Leptin and resistin may have some impacts on the fetal growth and development.

Topics: Adiponectin; Adult; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Resistin

The present study was planned to assess IGF-1, leptin and cholinesterase levels in maternal blood of both normoglycaemics and hyperglycaemics preeclampsia. Twenty five normotensive pregnant women at the time of delivery were selected in as group I and sub grouped according to blood glucose less than or more than 85 mg/dL as I A (<85mg/dL) and I B (>85mg/dL). Study group (group II, n=25) comprised of preeclamptic women and was further divided into group II A (<85mg/dL) and group II B (>85mg/dL). Routine biochemical investigations along with IGF-1, leptin and cholinesterase levels were analyzed in maternal and cord blood of preeclamptic and normotensive pregnant women. Serum IGF-1 levels were significantly lower in preeclamptic women and more so in those with hyperglycemia. Cord blood IGF-1 levels were nearly doubled in hyperglycemic preeclamptics as compared to normoglycemic preeclamptics. Leptin levels were higher in preeclamptic women and more in hyperglycemic preeclamptics. Cholinesterase levels were lowered in preeclamptic mothers and higher in hyperglycemics. Cord blood cholinesterase levels were reduced in preeclamptics, more so in hyperglycaemics as compared to group I. Diet recommendation, avoidance of excessive weight gain and healthy life style, exercise and nutritional interventions may be beneficial in these women.

Topics: Biomarkers; Blood Glucose; Cholinesterases; Diet; Female; Fetal Blood; Humans; Hyperglycemia; Insulin-Like Growth Factor I; Leptin; Life Style; Pre-Eclampsia; Pregnancy

Pre-eclampsia and eclampsia are parts of the broader spectrum of hypertensive disorders complicating pregnancy. This study aims to examine the association between serum inhibin and leptin levels and pre-eclampsia.. This study included 98 consecutive cases of pregnant women with pre-eclampsia, together with their 98 pregnant controls, matched for age, gestational week and time period of delivery. Maternal venous blood samples were obtained within 24h before delivery. In addition to serum inhibin and leptin, birth order, multiple pregnancy, maternal age, maternal overweight/obesity, maternal education, maternal smoking and family history of diabetes/hypertension, were examined as risk factors. Multivariate logistic regression analysis was performed.. At the univariate analysis, serum inhibin and leptin levels were significantly higher in cases vs.. Pre-eclampsia occurred more frequently in primiparous women, whereas overweight and obesity were also associated with pre-eclampsia. At the multivariate analysis, higher serum inhibin levels were associated with pre-eclampsia (multivariate OR=1.09, 95%CI: 1.03-1.17, p=0.004, increase per 0.1ng/mL). On the other hand, leptin was not independently associated with the occurrence of pre-eclampsia (multivariate OR=1.02, 95%CI: 0.95-1.09, p=0.631, increase per 10ng/mL).. Elevated serum inhibin levels seem to be associated with pre-eclampsia, reflecting placental dysfunction. Increased serum leptin levels may merely reflect an elevated maternal body mass index, which is a well-known risk factor for pre-eclampsia.

Topics: Case-Control Studies; Female; Humans; Inhibins; Leptin; Pre-Eclampsia; Pregnancy; Risk Factors

Leptin, an adipocyte-derived hormone, plays an important role in reproduction and angiogenesis. Studies examining leptin in preeclampsia are inconsistent, possibly because of small sample sizes and variability in sampling and outcome. We conducted a nested case-control study to examine associations between serum leptin (measured: 9-26 weeks gestation) and preeclampsia among 430 primiparous preeclamptic women and 316 primiparous normotensive controls from the Danish National Birth Cohort. Median (interquartile range) leptin concentrations were calculated. Associations between leptin and preeclampsia (blood pressure ≥140/90 mm Hg), term preeclampsia (preeclampsia and delivery ≥37 weeks gestation), or preterm preeclampsia (preeclampsia and delivery <37 weeks gestation) were examined using generalized linear models adjusting for body mass index, gestational age at blood draw, maternal age, smoking, and socio-occupational status. As leptin is increased in obese women and the risk of preeclampsia increases with body mass index, we used the Sobel test to examine whether leptin is a mediator of this relationship. After adjustments, leptin concentrations were significantly higher in women with preeclampsia (30.5 [24.6]; P=0.0117) and term preeclampsia (30.4 [24.9]; P=0.0228) compared with controls (20.9 [28.3]). There was no significant difference between preterm preeclampsia (30.6 [23.4]; P=0.2210) and controls. Leptin is a possible mediator of the association between body mass index and preeclampsia (P=0.0276). Leptin concentrations are higher in women with preeclampsia compared with normotensive controls and may mediate some of the relationship between body mass index and preeclampsia.

Topics: Adult; Biomarkers; Blood Pressure; Body Mass Index; Case-Control Studies; Denmark; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy

Preeclampsia (PE) is a pregnancy-specific syndrome with a complex, yet elusive, etiology. The production of a variety of factors probably implicated in diverse pathways may trigger endothelial dysfunction leading to PE pathogenesis. The aim of the present study was to investigate and compare the concentrations of leptin and interferon-gamma-inducible protein-10 (IP-10), factors characterized by inflammatory, immunomodulatory and angiogenic activities, and to evaluate their possible interaction in women with normotensive pregnancy and PE.. The study was carried out on a total of 58 pregnant women, 29 women with PE and 29 controls. Serum leptin and IP-10 levels were determined by enzyme-linked immunosorbent assay.. Serum leptin levels were significantly increased in women with PE compared to controls and this difference was stronger in women with severe PE (p < 0.001). Although IP-10 serum concentrations were elevated in our preeclamptic women, this difference was not statistically significant. No correlation was found between leptin and IP-10.. The results of the present study support a significant role of leptin in PE; however, this association was independent from serum IP-10 levels, suggesting that there is no crucial interplay between these two proteins in PE.

Topics: Adult; Body Mass Index; Chemokine CXCL10; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Severity of Illness Index

The aims of the present study were to compare plasma concentrations of the adiponectin, leptin, metalloproteinases (MMP9 and MMP2) and its tissue inhibitors (TIMP1 and TIMP2) in preeclamptic (PE) and healthy pregnant (HP) groups and correlate them.. A total of 105 pregnant women with pre-pregnancy body mass index (BMI) values ⩽ 30 kg/m(2) were enrolled for this study (59 PE and 46 HP). Biomarkers were measured using ELISAs.. Adiponectin (32%), leptin (45%), MMP2 (20%), TIMP1 (31%) and TIMP2 (23%) levels were higher in PE compared to HP (all P < 0.05). In addition there were positive correlations between adiponectin and MMP2 (r = 0.33; P = 0.03) and adiponectin and TIMP2 (r = 0.33; P = 0.03) in PE group, but not in HP.. Our findings show that adiponectin, leptin, MMP2, TIMP1 and TIMP2 levels are increased in PE and adiponectin may contribute to higher levels of MMP2 and TIMP2 in this disease.

Topics: Adiponectin; Adult; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Pre-Eclampsia; Pregnancy; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

To determine whether maternal preeclampsia influences insulin sensitivity (IS) or its biochemical markers in offspring.. Sixty children born from a preeclamptic pregnancy (PRE) and 60 matched control subjects born from a normotensive pregnancy (non-PRE) were studied at age 12 years. IS was estimated using the Quantitative Insulin Sensitivity Check Index (QUICKI), and serum concentrations of adiponectin, leptin, insulin-like growth factor (IGF)-1, IGF-2, IGF-binding protein-1 (IGFBP-1), sex hormone-binding globulin, lipids, and casual blood pressure (BP) were measured.. The mean values of QUICKI, serum adiponectin, leptin, IGF-1, IGF-2, IGFBP-1, and sex hormone-binding globulin did not differ between the PRE group and non-PRE group (P > .05 for all). The PRE subjects with the lowest IS (the lowest QUICKI tertile; n = 20) had significantly higher mean serum leptin (P = .007), triglyceride (P = .008), and IGF-1 (P = .005) levels and systolic BP (P = .019), and lower serum IGFBP-1 level (P = .007) compared with PRE subjects with higher QUICKI values (n = 40). Similarly, in logistic regression analysis, higher serum leptin (OR, 1.2; P = .009), triglyceride (OR, 1.2; P = .040), and IGF-1 (OR, 1.1; P = .031) levels and systolic BP (OR, 5.8; P = .024) were associated with low QUICKI in the PRE group.. Maternal preeclampsia did not produce decreased IS in offspring by age of 12 years. However, the offspring with the lowest IS had higher mean serum triglyceride level and systolic BP, suggesting that components of the metabolic syndrome may cluster in this subgroup.

Topics: Adiponectin; Biomarkers; Blood Pressure; Case-Control Studies; Child; Female; Humans; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Leptin; Male; Pre-Eclampsia; Pregnancy; Sex Hormone-Binding Globulin; Systole; Triglycerides

Adipokines contribute to the development of preeclampsia (PE), a severe pregnancy complication which increases the future risk for cardiovascular and metabolic disease in both mother and newborn. Pre-adipocyte factor-1 (Pref-1) was recently introduced as a novel antiangiogenic and antiadipogenic adipokine.. Pref-1 was quantified in patients with PE (n=51) and healthy pregnant controls (n=51) during pregnancy, as well as 6 months after delivery (study population 1). Furthermore, Pref-1 was investigated in the immediate peripartal period and the placenta in 40 healthy pregnant women undergoing elective cesarean section (study population 2).. In study population 1, median Pref-1 serum concentrations during pregnancy were significantly lower in women with PE (0.5 μg/l) as compared to healthy pregnant controls (0.7 μg/l) (p<0.001). Furthermore, Pref-1 serum concentrations were independently predicted by PE, leptin levels, and gestational age in this population. In both study populations, Pref-1 serum levels significantly decreased after delivery as compared to prepartal levels. Moreover, significant expression of Pref-1 was detected in placental tissue.. Maternal Pref-1 serum concentrations are significantly decreased in PE. The pathophysiological significance of this regulation needs to be studied in more detail in future experiments.

Topics: Adult; Calcium-Binding Proteins; Cesarean Section; Female; Gestational Age; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Membrane Proteins; Placenta; Pre-Eclampsia; Pregnancy

Preeclampsia (PE) is a pregnancy-specific disease, directly related to high rates of maternal-fetal morbidity and mortality worldwide. Upregulation of anti-angiogenic factors (soluble fms-like tyrosine kinase-1; sFLT-1 and soluble endoglin; sENG) have been suggested to trigger the maternal endothelial dysfunction observed in PE. Studies focusing on the role of adiponectin and leptin, in normal pregnancy as well as in complicated pregnancies, have revelated interesting findings due to the vascular actions of such adipokines. The aims of this study were to compare plasma concentrations of the adiponectin, leptin, sENG and sFLT-1 in preeclamptic (PE, n = 27) and healthy pregnant (HP, n = 36) and to evaluate possible correlations among these adipokines and anti-angiogenic factors. There were significant increases in all biomarkers in PE compared to HP (all p < 0.05). In PE group, there were positive strong correlations among adiponectin and leptin with sFLT-1 (r = 0.85 and r = 0.47, respectively) and sEng (r = 0.74 and r = 0.56, respectively). Moreover, we observed significantly correlation among body mass index (BMI) with adiponectin (r = -0.40) and with leptin (r = 0.51) in HP, but not in PE. Moreover, while a negative correlation between sFLT-1 and BMI (r = -0.60) was found in PE, no correlation was observed regarding sEng and BMI. In summary, our findings suggest the existence of a compensatory mechanism that occurs in an attempt to correct this angiogenic imbalance in order to restore the fetal development.

Topics: Adiponectin; Adult; Antigens, CD; Biomarkers; Body Mass Index; Case-Control Studies; Endoglin; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Receptors, Cell Surface; Vascular Endothelial Growth Factor Receptor-1; Young Adult

Early-pregnancy short sleep duration is predictive of gestational diabetes and preeclampsia; mechanisms for these associations are unknown. Leptin, an adipocyte-derived peptide involved in regulating food intake and energy expenditure, may play a role in these observed associations. Given inconsistent reports linking short sleep duration with leptin, and absence of studies among pregnant women, we examined the association of maternal sleep duration with plasma leptin in early pregnancy.. This cross-sectional study included 830 pregnant women. Plasma leptin was measured in samples collected around 13 weeks gestation. Sleep duration was categorized as: ≤5, 6, 7-8 (reference), and ≥9 hours. Differences in leptin concentrations across categories were estimated using linear regression. Analyses were completed for lean and overweight/obese women.. Overall, women with long sleep duration had elevated plasma leptin (p-value = 0.04). However, leptin concentrations were not statistically significantly elevated in women with a short sleep duration. There was no association of leptin with sleep duration among lean women. Among overweight/obese women, a U-shaped relation between leptin and sleep duration was observed: Mean leptin was elevated (β = 21.96 ng/ml, P < 0.001) among women reporting ≤5 hour of sleep compared with reference group; and women reporting ≥9 hours of sleep also had elevated leptin (β = 4.29 ng/ml, P = 0.09).. Short sleep duration, and to a lesser extent long sleep duration, were associated with elevated leptin among overweight/obese women. These data add some evidence to help understand mechanistic relationships of sleep duration with pregnancy complications.

Topics: Blood Glucose; Blood Pressure; Circadian Rhythm; Comorbidity; Cross-Sectional Studies; Diabetes, Gestational; Female; Humans; Leptin; Obesity; Overweight; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy Trimester, Second; Risk Factors; Secretory Rate; Sleep Initiation and Maintenance Disorders; Thinness; Washington

Obesity increases preeclampsia risk, and maternal dyslipidemia may result from exaggerated adipocyte lipolysis. We compared adipocyte function in preeclampsia with healthy pregnancy to establish whether there is increased lipolysis. Subcutaneous and visceral adipose tissue biopsies were collected at caesarean section from healthy (n=31) and preeclampsia (n=13) mothers. Lipolysis in response to isoproterenol (200 nmol/L) and insulin (10 nmol/L) was assessed. In healthy pregnancy, subcutaneous adipocytes had higher diameter than visceral adipocytes (P<0.001). Subcutaneous and visceral adipocyte mean diameter in preeclampsia was similar to that in healthy pregnant controls, but cell distribution was shifted toward smaller cell diameter in preeclampsia. Total lipolysis rates under all conditions were lower in healthy visceral than subcutaneous adipocytes but did not differ after normalization for cell diameter. Visceral adipocyte insulin sensitivity was lower than subcutaneous in healthy pregnancy and inversely correlated with plasma triglyceride (r=-0.50; P=0.004). Visceral adipose tissue had lower ADRB3, LPL, and leptin and higher insulin receptor messenger RNA expression than subcutaneous adipose tissue. There was no difference in subcutaneous adipocyte lipolysis rates between preeclampsia and healthy controls, but subcutaneous adipocytes had lower sensitivity to insulin in preeclampsia, independent of cell diameter (P<0.05). In preeclampsia, visceral adipose tissue had higher LPL messenger RNA expression than subcutaneous. In conclusion, in healthy pregnancy, the larger total mass of subcutaneous adipose tissue may release more fatty acids into the circulation than visceral adipose tissue. Reduced insulin suppression of subcutaneous adipocyte lipolysis may increase the burden of plasma fatty acids that the mother has to process in preeclampsia.

Topics: Adipocytes; Adult; Biopsy; Case-Control Studies; Female; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Isoproterenol; Leptin; Lipolysis; Lipoprotein Lipase; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Receptors, Adrenergic, beta-3; Subcutaneous Fat; Triglycerides

This study was designed to clarify the role of leptin and adiponectin in preeclampsia (PE) pathogenesis and different subtypes of preeclampsia.. This case control study was performed in 45 PE patients and 45 healthy controls matched for age, BMI, and ethnicity. Serum leptin and adiponectin levels were determined by enzyme linked immunosorbent assay (ELISA).. Maternal serum leptin and adiponectin were significantly higher in PE women than controls. Serum leptin was elevated in early onset preeclampsia (EOPE) and late onset preeclampsia (LOPE) compared to controls. Among PE patients, serum leptin was higher in EOPE than LOPE women. However, serum adiponectin was not different between EOPE and LOPE women. The serum leptin was significantly higher in severe PE than mild PE. The serum adiponectin was significantly elevated in severe PE compared to controls. Significant positive correlation was observed between leptin and adiponectin and also between leptin and BMI in controls. Moreover significant positive correlation was observed between adiponectin and BMI in PE patients and controls.. The present study showed that serum leptin level may play a significant role as a biomarker to differentiate early and late onset PE and also its relation to BMI and severity of disease.

Topics: Adiponectin; Adult; Biomarkers; Case-Control Studies; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Severity of Illness Index; Young Adult

miRNAs are small non-coding RNAs important for the regulation of mRNA in many organs including placenta. Adipokines and specifically leptin are known to be dysregulated in preeclampsia, but little is known regarding their regulation by miRNAs during pregnancy.. We performed high-throughput sequencing of small RNAs in placenta from 72 well-defined patients: 23 early-onset preeclampsia (PE), 26 late-onset PE and 23 controls. The regulation of some miRNAs was confirmed on qRT-PCR. Maternal circulating levels and placental mRNA of leptin, resistin and adiponectin were measured using Bio-Plex and qRT-PCR.. We found that miR-1301, miR-223 and miR-224 expression was downregulated in early-onset PE, but not in late-onset PE, compared to controls. In silico analysis predicted the leptin gene (LEP) to be a target for all three miRNAs. Indeed, we found significant correlation between maternal circulating levels of leptin and placental LEP expression. In addition, we found a significant inverse correlation between maternal circulating leptin/placental LEP expression and placental miR-1301 expression levels. Interestingly, placental expression of miR-1301 was also correlated with newborn weight percentile and inversely correlated with both maternal systolic and diastolic blood pressure prior to delivery.. Our results confirm that placenta is a major site of LEP expression during pregnancy. It further suggests that miR-1301 could be involved in the regulation of leptin during pregnancy and may play a role in early-onset PE.. miR-1301 is dysregulated in early-onset preeclampsia and could possibly play a role in the regulation of leptin during pregnancy.

Topics: Adolescent; Adult; Blood Pressure; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; MicroRNAs; Placenta; Pre-Eclampsia; Pregnancy; Young Adult

To explore the differentially expressed genes(DEG)involved in the pathogenesis of preeclampsia (PE).. The gene expression profiles of placental tissues from 7 severe PE patients and 7 preterm controls from June to December 2012 were assessed using microarray. Gene ontology (GO) enrichment analysis and pathway analysis were performed to explore the genes and pathways involved in the pathogenesis of PE. Four DEG involved in these biological processes were further verified by quantitative real-time PCR.. A total of 308 transcripts were significantly differentially expressed. Of these DEG, 81 genes(LEPTIN, PAPPA2, CRH, PLIN2, INHA, BCL6, FLT1, CCR7, etc) were up-regulated, and 227 genes (CXCL12, CXCL9, etc)were down-regulated. GO enrichment analysis indicated that the top 3 GO molecular functions were immune response (GO: 0006955, 17 DEG), positive regulation of apoptosis (GO: 0043065, 11 DEG) and inflammatory response (GO: 0006954, 11 DEG). Pathway analysis showed that the top 3 pathways were cell adhesion molecules (11 DEG), cytokine- cytokine receptor interaction (11 DEG), chemokine signaling pathway (8 DEG). Many genes (LEP, FLT1, TFRC, SH3PXD2A, CYP11A1, SEPP1, and so on) involved in oxidative stress were found to be significantly changed. Of these genes, LEP were significantly up- regulated with a fold change of 61.5. The fold changes of FLT1, SH3PXD2A, SEPP1, CYP11A1, TFRC were 8.6, 2.2, -2.0, 2.7 and -2.8. Four DEG involved in oxidative stress were further verified by quantitative real-time PCR.. A DEG signature was identified in severe preeclampsia placentas compared with normal controls. The DEG mainly involved in the molecular mechanisms of immune response, oxidative stress and inflammatory response, and were closely associated with the pathogenesis of PE.

Topics: Down-Regulation; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Leptin; Oligonucleotide Array Sequence Analysis; Placenta; Pre-Eclampsia; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; Up-Regulation

The primary mechanism underlying pre-eclampsia (PE) remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n = 16) versus normal placentas (n = 16). Our results showed that many CpG sites close to the transcriptional start site (TSS) of LEP gene were hypomethylated in placentas from pregnancies with PE compared with those of in controls, including the TSS position (p = 0.001), the binding sites of Sp1 (p = 1.57×10(-4)), LP1 (p = 0.023) and CEBPα (p = 0.031). Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBPα co-transfection had a role in the regulation of gene expression. Our results indicated the aberrant LEP promoter methylation was involved in the development of PE. We did not find a significant methylation differences between groups in the promoter region of SH3PXD2A, however, a CGI region in the gene body (CGI34) presented a higher methylation in preeclamptic placentas (p = 1.57×10(-4)), which might promote the efficiency of gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis of PE through its role in the regulation of trophoblast cell invasion in the period of placenta formation.

Topics: Adaptor Proteins, Vesicular Transport; Adult; Case-Control Studies; Cell Line; Computational Biology; DNA Methylation; Female; Gene Expression Profiling; Genes, Reporter; Humans; Leptin; Luciferases; Oligonucleotide Array Sequence Analysis; Pre-Eclampsia; Pregnancy; Reproducibility of Results; RNA, Messenger; Transcription, Genetic; Transfection; Up-Regulation

Previous studies have shown markedly lower birth weight among infants of South Asian origin compared with those of White European origin. Whether such differences mask greater adiposity in South Asian infants and whether they persist across generations in contemporary UK populations is unclear. Our aim was to compare birth weight, skinfold thickness and cord leptin between Pakistani and White British infants and to investigate the explanatory factors, including parental and grandparental birthplace.. We examined the differences in birth weight and skinfold thickness between 4649 Pakistani and 4055 White British infants born at term in the same UK maternity unit and compared cord leptin in a subgroup of 775 Pakistani and 612 White British infants.. Pakistani infants were lighter (adjusted mean difference -234 g 95% CI -258 to -210) and were smaller in both subscapular and triceps skinfold measurements. The differences for subscapular and triceps skinfold thickness (mean z-score difference -0.27 95% CI -0.34 to -0.20 and -0.23 95% CI -0.30 to -0.16, respectively) were smaller than the difference in birth weight (mean z-score difference -0.52 95% CI -0.58 to -0.47) and attenuated to the null with adjustment for birth weight (0.03 95% CI -0.03 to 0.09 and -0.01 95% CI -0.08 to 0.05, respectively). Cord leptin concentration (indicator of fat mass) was similar in Pakistani and White British infants without adjustment for birth weight, but with adjustment became 30% higher (95% CI 17% to 44%) among Pakistani infants compared with White British infants. The magnitudes of difference did not differ by generation.. Despite being markedly lighter, Pakistani infants had similar skinfold thicknesses and greater total fat mass, as indicated by cord leptin, for a given birth weight than White British infants. Any efforts to reduce ethnic inequalities in birth weight need to consider differences in adiposity and the possibility that increasing birth weight in South Asian infants might inadvertently worsen health by increasing relative adiposity.

Topics: Adipose Tissue; Adult; Birth Weight; Body Mass Index; Diabetes, Gestational; Female; Fetal Blood; Gestational Age; Glucose Intolerance; Hospitals, Maternity; Humans; Infant, Newborn; Leptin; Pakistan; Pre-Eclampsia; Pregnancy; Pregnant Women; Prospective Studies; Regression Analysis; Skinfold Thickness; Surveys and Questionnaires; United Kingdom; White People

To assess maternal leptin levels as a marker for preeclampsia (PE) and to explore the possibility of leptin being a marker of severity of preeclampsia.. Comparative prospective study was conducted among a total of 72 pregnant women at 28-38 weeks of gestation. They were divided into two groups (control and study) according to the absence or presence of clinical parameters of preeclampsia. Leptin was measured for both groups at the time of presentation, once weekly and at the termination of pregnancy.. Leptin levels were found to be significantly higher among all preeclampsia patients when compared to the control group; whether at admission or at the time of delivery. Mean serum leptin level at admission in control group was 9.8 ng/ml versus 10.9 ng/ml in mild cases and 17.6 ng/ml in severe cases. At the time of delivery, mean serum leptin in control group decreased to 4.7 ng/ml while in preeclampsia patients it increased up to 22 ng/ml in mild cases and 42.6 ng/ml in severe cases. ROC curve analysis has shown that a cut off value >13.7 ng/ml can be used to detect presence of preeclampsia with a sensitivity of 91% and specificity 100% while a cut off value >22.5 ng/ml can be used to detect severity of preeclampsia with a sensitivity of 85% and specificity 100%.. Maternal serum leptin is significantly elevated in preeclampsia, also it can be used as a marker for the presence of preeclampsia and to differentiate patients with mild preeclampsia from those with severe disease.

Topics: Adult; Analysis of Variance; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Leptin; Pre-Eclampsia; Pregnancy; Prospective Studies; Sensitivity and Specificity

The aim of the present study was to assess leptin/adiponectin ratio in preeclamptic patients compared with normal pregnant women. A cross-sectional study was designed. The study population consisted of 30 preeclamptic patients and 30 healthy pregnant women. Serum levels of total leptin and adiponectin were assessed using commercially available enzyme-linked immunosorbent assay methods. The one-way ANOVA and Student's t tests and Pearson's correlation analysis were used for statistical calculations. Levels of leptin and adiponectin were also adjusted for BMI. A p-value < 0.05 was considered statistically significant. The leptin/adiponectin ratio was increased significantly in preeclamptic patients. The leptin/adiponectin ratio was significantly higher in severe preeclamptic patient than in mild preeclampsia. Adjusted leptin/adiponectin ratio was also significantly increased in preeclamptic patients than in normal pregnant women. The findings of the present study suggest that the leptin/adiponectin ratio was increased in preeclamsia and imbalance between the adipocytokines could be involved in the pathogenesis of preeclampsia.

Topics: Adiponectin; Adult; Analysis of Variance; Bangladesh; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy

Although pregnancies associated with hyperinsulinemia and altered placental angiogenic and inflammatory factors are at increased risk for developing preeclampsia, the effects of euglycemic hyperinsulinemia on placental factors and blood pressure regulation during pregnancy are unclear. We hypothesized that chronic hyperinsulinemia results in increased placental soluble fms-like tyrosine kinase 1(sFlt-1) and tumor necrosis factor α (TNF- α) levels and hypertension in pregnant rats.. On gestational day (GD) 14, Sprague-Dawley rats were assigned as normal pregnant or pregnant + insulin. Insulin was infused subcutaneously by osmotic minipump for 5 days at a dose of 1.5 mU/kg/min. Those rats receiving insulin were supplemented with 20% glucose in drinking water to maintain euglycemia. On GD 19, mean arterial pressure (MAP) and heart rate (HR) were assessed in conscious rats by indwelling carotid catheters, followed by collections of blood, placentas, and fetuses. In addition to placental sFlt-1 and TNF-α levels, circulating insulin, glucose, leptin, cholesterol, triglyceride, and free fatty acid concentrations were measured.. MAP was higher in pregnant + insulin vs. normal pregnant rats; however, HR was similar between groups. Although litter size and placental weight were comparable, fetuses from pregnant + insulin rats were heavier. Importantly, circulating insulin concentration was elevated in the pregnant + insulin group, with no change in glucose level. Moreover, circulating leptin, cholesterol, triglyceride, and free fatty acid concentrations were increased in the pregnant + insulin group. There were no differences in placental sFlt-1 and TNF-α concentrations between groups.. In summary, sustained euglycemic hyperinsulinemia, comparable with insulin levels in preeclamptic women, can raise blood pressure in pregnancy independent of recognized placental factors associated with preeclampsia.

Topics: Animals; Biomarkers; Blood Pressure; Cholesterol; Disease Models, Animal; Female; Glucose; Heart Rate; Hyperinsulinism; Hypertension; Insulin; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Triglycerides; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor-1

HIV-associated preeclampsia reflects a combination of opposing influences on the immune status. The adipocyte hormone leptin has been implicated in the pathophysiology of preeclampsia and in enhancing immunity. This study is the first, to our knowledge, to determine whether leptin levels in the placenta differ between HIV-associated normotensive and preeclamptic pregnancies. The study also compares leptin levels between the exchange and conducting areas of the placenta.. Pregnant women were recruited antenatally and grouped as follows: normotensive HIV uninfected (n=30), normotensive HIV infected (n=60), preeclamptic HIV uninfected (n=30) and preeclamptic HIV infected (n=60). Anthropometric data were collected and placental leptin was analysed by immunohistochemistry and ELISA.. Leptin levels were similar in the central and peripheral regions of the placenta. Leptin immunoreactivity was observed amongst the different trophoblast cell populations. Both ELISA and immunohistochemistry of the placental exchange villi indicated that leptin levels were higher in preeclampsia compared to normotensive pregnancies (p<0.001). HIV status had no effect on leptin levels but levels were higher in participants on highly active antiretroviral treatment (HAART) compared to those on prophylaxis for prevention of mother to child transmission (PMTCT) with normotensive (p=0.006) and preeclamptic (p=0.002) pregnancies. The area of immunostaining was greater in the exchange compared to the conducting villi in HIV infected and uninfected preeclampsia.. This novel study establishes an elevation of leptin in preeclamptic placentae, irrespective of HIV status. Leptin elevation was not focal in that it occurred in both central and peripheral regions of the preeclamptic placenta. This suggests a role of leptin in the pathophysiology of preeclampsia.

Topics: Adult; Antiretroviral Therapy, Highly Active; Chorionic Villi; Female; HIV Infections; Humans; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious

The objective of this study is to show that pregnancy is a unique immune phenomenon because the feto-placental unit can develop without being attacked by the maternal immune system despite the admixing of maternal and fetal cells. There is a growing body of evidence that regulatory T cells (Tregs) act as modulators of vascular homeostasis. The aim of this study was to evaluate the role of interleukin-10 polymorphism along with leptin in the pathogenesis of preeclampsia. The study was carried out on 20 primigravida pregnant women with preeclampsia and 20 normal primigravida pregnant women. Blood samples sent for laboratory tests showed the presence of serum leptin, which was determined by DRGLeptin sandwich (Enzyme-linked immunosorbent assay (ELISA) technique) (EIA-2395; DRG International, Inc., Mountainside, NJ, USA) and serum IL-10 was determined by ELISA (Genzyme, Cambridge, MA, USA). The detection of IL-10 polymorphism was done by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. The results of this study show that there was a significant difference between the frequency of genotype in patients and control group with regard to GG genotype, AA genotype, A allele, and G allele (P < .05) However, it was not significant with regard to the frequency of AG genotype (P > .05). The serum leptin was found to be significantly higher in preeclampsia group and with a more significant increase in AA genotype.

Topics: Adipose Tissue; Adult; Alleles; Body Mass Index; Case-Control Studies; Female; Genotype; Humans; Interleukin-10; Leptin; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

In pre-eclampsia, placental leptin is up-regulated and leptin is elevated in maternal plasma. To investigate potential epigenetic regulation of the leptin (LEP) gene in normal and complicated pregnancy, DNA methylation was assessed at multiple reported regulatory regions in placentae from control pregnancies (n=111), and those complicated by early onset pre-eclampsia (EOPET; arising <34 weeks; n=19), late onset pre-eclampsia (LOPET; arising ≥34 weeks; n=18) and normotensive intrauterine growth restriction (nIUGR; n=13). The LEP promoter was hypomethylated in EOPET, but not LOPET or nIUGR placentae, particularly at CpG sites downstream of the transcription start site (-10.1%; P<0.0001). Maternal plasma leptin was elevated in EOPET and LOPET (P<0.05), but not nIUGR, compared with controls. EOPET cases showed a trend towards biallelic LEP expression rather than skewed allelic expression observed in control placentae, suggesting that loss of normal monoallelic expression at the LEP locus is associated with hypomethylation, leading to increased overall LEP expression.

Topics: 5' Untranslated Regions; Alleles; Base Sequence; CpG Islands; DNA Methylation; Female; Gestational Age; Humans; Leptin; Molecular Sequence Data; Placenta; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Promoter Regions, Genetic

The aim of this study was to investigate the relationship between the leptin receptor (LEPR) polymorphism/serum leptin level and preeclampsia. The prevalence of a single nucleotide polymorphism in the LEPR gene exon 14 at -656 and the serum leptin concentrations in 97 preeclamptic pregnant mothers were compared to those of 110 healthy controls. The Lys656Asn genotype and Lys656Asn + Asn656Asn frequencies in the LEPR gene were significantly more prevalent in preeclampsia mothers than in controls (P < 0.05). The serum leptin levels of preeclampsia cases were significantly higher than those of controls. In addition, there were higher serum leptin levels in individuals with the GC + CC genotype both in the total cohort and in women with preeclampsia than in those with the GG genotype. Our findings suggest that the Lys656Asn polymorphism is a functional variant in the LEPR, which can affect the interaction of leptin and its receptor. Furthermore, high leptin level and the LEPR variant are risk factors for preeclampsia in Chinese women.

Topics: Adult; Case-Control Studies; China; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Mutation, Missense; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Receptors, Leptin

Leptin is an adipokine which has a direct relationship to obesity. Our aim was to measure this hormone in pregnant women at three months intervals throughout their pregnancies to determine the serum value of those who developed preeclampsia.. We followed 19 women (median age 24.8 +/- 5.7 years) with pre-gestational Body Mass Index (BMI) less than 25 kg/m2, 21 (median age 26.1 +/- 4.6 years) with BMI higher than 25 kg/m2 and 16 (median age 30.9 +/- 5.8 years) with Gestational Diabetes Mellitus (GDM) (median age 30.9 +/- 5.8 years), recruited in the 1st trimester of pregnancy. Serum levels of leptin were measured with radioimmunoassay (RIA) technique.. In the first trimester of pregnancy leptin levels showed statistically significant differences between normal weight and overweight-obese women (p < 0.001), diabetic women (p < 0.05) and the subgroup of preeclamptic women (p < 0.001). For those women with PGBMI > or = 40 kg/m2 and leptin > or = 40 ng/ml in the second trimester, the Odds Ratio (OR) to develop preeclampsia was of 47.95% CI (4.1-527.2). Analyzing leptin values with ROC curves, the greatest area under the curve (AUC) was for leptin in the second trimester (0.773, CI: 0.634-0.911).. Women with morbid obesity (BMI > or = 40 kg/m2) had significantly higher levels of serum leptin (p < 0.01) and a value of 40 ng/ml of this hormone seems to be predictive of developing preeclampsia in this group of patients.

Topics: Adult; Body Mass Index; Diabetes, Gestational; Female; Humans; Leptin; Obesity; Overweight; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prognosis; Risk Factors; Sensitivity and Specificity

Constitutive androstane receptor (CAR) has been reported to decrease insulin resistance, while obesity and insulin resistance may also be involved in the pathogenesis of preeclampsia. We examined whether a CAR ligand, 1,4-bis(2-(3,5-dichloropyridyloxy)) benzene (TCPOBOP), can ameliorate the signs of preeclampsia in high-fat diet (HFD)-induced obese pregnant mice to examine a possibility of CAR as a therapeutic target. We employed six groups including non-pregnant, HFD-fed or control diet-fed pregnant mice with or without TCPOBOP treatment (n=6). In HFD pregnant mice, insulin resistance increased with increasing expression of gluconeogenic and lipogenic genes and abnormal adipocytokine levels. TCPOBOP treatment, which was once-weekly intraperitoneal injections (0.5 mg/kg) and started at day 0.5 of pregnancy, improved glucose tolerance with significant changes of gluconeogenic, lipogenic and adipocytokine genes. HFD pregnant mice had hypertension and proteinuria, while TCPOBOP treatment ameliorated these signs. Our data suggested CAR might be a potential therapeutic target for obese preeclampsia patients with insulin resistance.

Topics: Adiponectin; Animals; Blood Glucose; Body Weight; Constitutive Androstane Receptor; Diet, High-Fat; Female; Gene Expression; Gluconeogenesis; Gonadal Steroid Hormones; Hydrocortisone; Insulin; Leptin; Lipogenesis; Male; Mice; Mice, Inbred ICR; Obesity; Pre-Eclampsia; Pregnancy; Pyridines; Receptors, Cytoplasmic and Nuclear

Leptin is known to be elevated in pre-eclampsia/ pregnancy induced hypertension (PE/PIH). However the reports on the association of leptin receptor (LEPR) c.668A>G polymorphism with PE/PIH are inconsistent.. LEPR c.668A>G polymorphism was studied in a cohort of women with PE/PIH (N = 61) and normotensive pregnancies (N = 40) by polymerase chain reaction / restriction fragment length polymorphism. Genotype and allele frequencies were in Hardy-Weinberg equilibrium within both groups (Chi square test). Allele and genotype frequencies were not significantly different between PE/PIH and normotensive pregnancies (Chi square test). Leptin levels (Kruskal Wallis analysis of variance) and leptin/body mass index (one way analysis of variance) were not significantly different between genotypes within each group. However, leptin (Mann Whitney U test) and leptin normalised to body mass index (unpaired t test) were significantly higher in PE/PIH women homozygous and heterozygous for the G668 allele than in respective normotensives.. Whether the leptin receptor c.668A>G polymorphism increases the risk of developing PE/PIH in Sri Lankan women remains inconclusive in view of the smaller sample studied. However leptin levels in PE/PIH appeared to be modulated by this polymorphism.

Topics: Body Mass Index; Case-Control Studies; Cohort Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Hypertension, Pregnancy-Induced; Leptin; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Receptors, Leptin; Sri Lanka

Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR), and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (< 32 weeks) and with a birth weight too low for their gestational age (-1SDS) and a normal postnatal growth (>-1SDS at 3 months post term; AGA). The SGA individuals were not only lighter at birth, but also had a smaller length (P=3.3x10 (-13) ) and head circumference at birth (P=4.1x10 (-13) ). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5%, 47.5%, 79.4% and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non epigenetic mechanisms that may lead to similar later health outcomes.

Topics: DNA Methylation; Epigenesis, Genetic; Female; Fetal Growth Retardation; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Insulin-Like Growth Factor II; Leptin; Male; Pre-Eclampsia; Pregnancy; Smoking; Starvation

To explore the changes of IGF-I and leptin levels in serum and placental tissue of prceclampsia patients, and to study the associativity of IGF-I and leptin at the onset and in the development of prceclampsia further.. The levels of IGF-I and leptin in serum and placental tissue of 80 patients with prceclampsia and 50 normal pregnancy were detected with ELISA and immunohistochemistry.. The serum IGF-I level of mild and severe prceclampsia was significantly lower than that of normal pregnancy group (P<0.05), and the serum leptin level of mild and severe prceclampsia was significantly lower than that of normal pregnancy group (P<0.05). The serum IGF-I level in severe prceclampsia group was lower than that in mild prceclampasia and the serum leptin level in severe prceclampsia was higher than that in mild prceclampsia ( P<0.05). There were significantly difference in the expression of IGF-I and leptin among normal pregnancy group, mild and severe prceclampsia group (P<0.05).. The level of IGF-I and leptin may be involved in the pathogenesis and development of prceclampsia and can be a index to test the prognosis of prceclampsia patient.

Topics: Adult; Female; Humans; Insulin-Like Growth Factor I; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Prognosis; Young Adult

Conditions resulting in insulin resistance, as well as metabolic, immune, and angiogenic perturbations, have been associated with an increased risk of preeclampsia (PE). Our purpose was to assess whether the adipose tissue-secreted hormones adiponectin, which has immune-modulating, metabolic, and angiogenic properties, and leptin, which reflects overall fat mass, are associated with PE risk. We performed a case-control design study within a hospital-based cohort of 368 pregnant women (106 with PE and 262 controls; mean age, 26.6 ± 6.8 years; mean gestational age at admission, 38.2 ± 2.8 weeks) between March 2005 and August 2007 at the Hospital of Pennsylvania University. Serum adiponectin and leptin were measured by radioimmunoassay. Statistical analysis of data was performed using simple and multiple regression analyses. No significant differences in adiponectin or leptin levels between preeclamptic and control pregnant women emerged in univariate analyses (P = .57 and P = .15, respectively). Among preeclamptic women, there were also no differences in adipokines between those with mild and severe disease. Serum adiponectin and leptin were not associated with higher risk of PE before and after adjustment for maternal age, race, primigravida, smoking status, body mass index at screening, gestational age at admission, history of PE, chronic hypertension, and gestational diabetes (odds ratio, 0.93; 95% confidence interval, 0.83-1.04 and odds ratio, 1; 95% confidence interval, 0.97-1.03, respectively). Maternal serum adiponectin and leptin levels, drawn at the time of PE diagnosis, were not associated with PE.

Topics: Adiponectin; Adult; Case-Control Studies; Cohort Studies; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Risk Factors; Severity of Illness Index; Young Adult

In this study, we determined circulating levels of C-reactive protein, several cytokines, chemokines, adhesion molecules and angiogenic factors along with those of leptin in healthy non-pregnant and pregnant women and preeclamptic patients, and investigated whether serum leptin levels were related to the clinical characteristics and measured laboratory parameters of the study participants.. Sixty preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Levels of leptin and transforming growth factor (TGF)-beta1 in maternal sera were assessed by ELISA. Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by multiplex suspension array. Serum C-reactive protein (CRP) concentrations were measured by an autoanalyzer. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied.. There were significant differences in most of the measured laboratory parameters among the three study groups except for serum IL-1beta and TGF-beta1 levels. Serum leptin levels were significantly higher in preeclamptic patients and healthy pregnant women than in healthy non-pregnant women. Additionally, preeclamptic patients had significantly higher leptin levels as compared to healthy pregnant women. Serum leptin levels were independently associated with BMI in healthy non-pregnant women. In healthy pregnant women, both BMI and serum CRP concentrations showed significant positive linear association with leptin levels. There were significant positive correlations between serum leptin concentrations of healthy pregnant women and systolic blood pressure, as well as serum levels of IP-10, while their serum leptin levels correlated inversely with fetal birth weight. In preeclamptic patients, a significant positive correlation was observed between serum concentrations of leptin and IP-10. Furthermore, elevated serum leptin level and sFlt-1/PlGF ratio had an additive (joint) effect in the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone.. Simultaneous measurement of leptin with several inflammatory molecules and angiogenic factors in this study enabled us to investigate their relationship, which can help to understand the role of circulating leptin in normal pregnancy and preeclampsia.

Topics: Algorithms; Angiogenic Proteins; Biomarkers; Birth Weight; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cell Adhesion Molecules; Chemokine CXCL10; Chemokines; Cytokines; Female; Humans; Infant, Newborn; Leptin; Male; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Sensitivity and Specificity; Vascular Endothelial Growth Factor Receptor-1

To evaluate the association of serum leptin concentrations and polymorphisms of G1019A and A223G of leptin receptor gene (LEPR) with severe pre-eclampsia. MEHTODS: A case-control study was carried out in 207 patients with severe pre-eclampsia (SPE group) and 252 healthy pregnant women (control group) during the third trimester of pregnancy. The serum leptin was determined by enzyme-linked immunosorbent assay. The polymorphisms of LEPR gene G1019A and A223G were detected by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) analysis. Miettinen's test was used to estimate the odds ratios (OR) and 95% confidence intervals (CI).. (1) In severe pre-eclampsia group, serum leptin levels and rate of premature infant birth were significantly higher than that in normal pregnant women, and birth weight was lower than that in controls (P<0.01). (2) The frequencies of GA genotype and G allele for LEPR gene G1019A in SPE group (33.8% and 20.3%) were markedly higher than that in controls (19.8% and 15.1%) (P<0.01), and the carriers of GA genotype and G allele were more frequent in SPE group than in control group, resulting in an OR 2.04 (95%CI: 0.77-5.42) and 1.43 (95%CI: 1.02-2.01) to develop severe pre-eclampsia, compared with carriers of AA genotype and A allele. (3) AG genotype and A allele frequencies of LEPR gene A223G in SPE group (19.3% and 12.6%) were significantly lower than that in controls (34.5% and 19.2%) (P<0.01), resulting in an OR of 0.46 (95%CI: 0.30-0.71) and 0.60 (95%CI: 0.42-0.87) to develop severe pre-eclampsia, compared with subjects with GG genotype and G allele. (4) The "1019AA+223AG" genotype frequency was significantly lower in SPE group (6.8%) than in controls (24.6%) (P<0.01), resulting in an OR of 0.22 (95%CI: 0.12-0.39) to develop severe pr-eclampsia, while the "1019AA+223AG" was significantly higher in SPE group (22.2%) than in controls (11.9%) (P<0.05), resulting in an OR of 2.10 (95%CI: 0.78-3.45) to develop severe pre-eclampsia. (5) No significant differences were found in SBP, DBP, BMI and serum leptin levels in subjects with different genotypes in the two groups (P>0.05).. Elevated serum leptin level and LEPR gene G1019A and A223G polymorphisms might play a role in severe pre-eclampsia, while the level of serum leptin was not associated with genotypes of LEPR gene G1019A and A223G polymorphisms. The genotypes GA and "1019AA+223AG"of G1019A may be genetic susceptibility factors to severe pre-eclampsia.

Topics: Adult; Alleles; Blood Pressure; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy; Receptors, Leptin; Young Adult

Contemporary scientific data show that there is a link between insulin resistance and preeclampsia. Many features of the insulin resistance syndrome are common with this condition. These include hypertension, hyperinsulinemia, glucose intolerance, obesity and lipid abnormalities. The women with preeclampsia are more insulin resistant than those with normal pregnancy. The surrogate markers of insulin resistance like leptin, TNF-alpha, tissue plasminogen activator, SHBG etc are also changed in preeclampsia. Whether these changes are connected with etiology or with the pathogenesis of preeclampsia is still not clear.

Topics: Female; Humans; Insulin; Insulin Resistance; Leptin; Pre-Eclampsia; Pregnancy; Tissue Plasminogen Activator; Tumor Necrosis Factor-alpha

Prophylaxis with low-dose aspirin may reduce the risk of pre-eclampsia (PE) if introduced in first trimester. The performance of first trimester maternal serum screening for PE using free leptin index (fLI) and PAPP-A, where fLI = leptin/leptin soluble receptor was studied.. First trimester serum samples from 126 PE pregnancies and 289 control pregnancies were studied. fLI and PAPP-A were converted into gestational age and maternal weight independent log MoM values of PAPP-A and fLI. The screening performance of markers was studied by receiver-operator-characteristics curves. The performance of population screening was estimated by Monte Carlo simulation.. fLI was significantly (p < 0.001) elevated [mean log MoM 0.2165 (SD: 0.2604)] compared to controls [mean log MoM -0.0368 (SD: 0.3132)] and PAPP-A was significantly (p < 0.001) reduced [mean log MoM -0.0133 (SD: 0.2661)] compared to controls [mean log MoM 0.0474 (SD: 0.2521)] in PE pregnancies. There was no correlation between fLI and PAPP-A in control or PE pregnancies. Combined fLI and PAPP-A screening for PE had estimated population detection rates of 22% and 35% for false positives rates of 6% and 12%, respectively.. Combining PAPP-A and fLI improves screening performance for PE compared to single marker screening.

Topics: Adult; Biomarkers; Case-Control Studies; Female; Gestational Age; Humans; Leptin; Mass Screening; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Prenatal Care; Risk Factors

Circulating angiogenic factors have been shown to be important in the pathophysiology of pre-eclampsia. Blood levels of adipocytokines differ in pre-eclampsia relative to controls and may also play an important role in disease pathogenesis. Differences in the circulating levels of these molecules were compared between matched normotensive controls and women with pre-eclampsia with onset before or at/after 32 weeks, and according to whether the women were of normal weight (18.5 < body mass index < 25) or overweight.. A cross-sectional study of 110 pregnant Japanese women who visited the Department of Obstetrics and Gynecology, Okayama University Hospital, Okayama, Japan.. Tertiary referral centre serving 2000 births.. Serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin (sEng), adiponectin and leptin were measured in women with pre-eclampsia and in normotensive controls matched for age, gestational week, parity and body mass index. Main outcome measures Serum levels of sFlt-1, PlGF, the sFlt-1/PlGF ratio, sEng, adiponectin and leptin.. The sFlt-1/PlGF ratio in early-onset pre-eclampsia was significantly higher than that in late-onset pre-eclampsia (112.0 +/- 30.2 versus 45.4 +/- 43.8, P = 0.037). There was a significant elevation of leptin in both subtypes relative to controls (early: 58.6 +/- 18.3 ng/ml versus 26.0 +/- 6.7 ng/ml, P = 0.001; late: 39.5 +/- 9.2 ng/ml versus 22.0 +/- 4.3 ng/ml, P = 0.005), but adiponectin was increased only in late-onset pre-eclampsia (36.5 +/- 13.4 microg/ml versus 12.0 +/- 4.3 microg/ml, P = 0.003). Significant differences in angiogenic factors and adiponectin were found between normal and overweight women only in late-onset pre-eclampsia.. These data suggest that there are different profiles of angiogenic factors and adipocytokines between women who develop early- and late-onset pre-eclampsia.

Topics: Adipokines; Adiponectin; Adult; Angiogenesis Inducing Agents; Blood Pressure; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Gestational Age; Humans; Leptin; Overweight; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Young Adult

We measured first trimester plasma leptin concentrations in 37 women who subsequently developed pre-eclampsia and 53 normotensive controls to determine the interrelation between leptin and body mass index (BMI) in both groups. We further investigated the association between the risks for pre-eclampsia with maternal leptin levels.. Bloods samples were collected at 13 weeks. Non-parametric tests, Spearman's correlation, linear regression analysis and multiple logistic regression analysis were applied in our data.. 1 kg/m(2) increase in pre-pregnancy BMI was related to a 2.747 (95% CI: 3.242-2.252) ng/ml rise in leptin concentration among cases and 2.502 (95% CI: 2.873-2.131) ng/ml rise in leptin concentrations among controls. Increased leptin concentration (>or=25.3 ng/ml ) in lean women is associated with a 18.8-fold increased risk of pre-eclampsia (adjusted OR: 18.8, CI: 1.8-194, p = 0.014 ). Leptin treated as a continuous variable is a significant predictor of pre-eclampsia (adjusted OR: 1.08, CI: 1.018-1.133, p = 0.009).. Increased leptin concentration can definitely contribute to the prediction of pre-eclampsia in lean women, but this is not the case in overweight women. Further research in terms of longitudinal case-control studies is required to clarify the predictive value of pre-eclampsia.

Topics: Adult; Biomarkers; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Logistic Models; Maternal Age; Odds Ratio; Overweight; Parity; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Risk Factors; Smoking

Visceral fat accumulation stimulates the production of adipocytokines in patients with metabolic syndrome. Excess body weight gain during pregnancy is a risk factor for preeclampsia. To evaluate whether the pathogenesis of preeclampsia is similar to that of metabolic syndrome, we measured plasma adipocytokine concentrations and investigated the association between plasma adiponectin concentrations and body weight gain or endothelial function in preeclamptic women. We investigated 15 preeclamptic and 17 women with uncomplicated pregnancies. Women with preeclampsia had significantly lower plasma concentrations of adiponectin (10.2+/-2.0 vs. 7.3+/-2.2 microg ml(-1), P<0.01), but higher concentrations of leptin, plasminogen activator inhibitor-1, interleukin-6, vascular cell adhesion molecule-1, E-selectin and C-reactive protein. Plasma triglyceride levels were significantly higher in preeclamptic patients, but the levels of other lipids did not differ significantly between the two groups. We found that flow-mediated vasodilation was significantly decreased in preeclamptic women compared with controls (10.6+/-6.4 vs. 3.8+/-2.0%, P<0.001). Plasma adiponectin concentrations correlated negatively with body mass index (r=-0.50, P<0.05) and body weight gain during pregnancy (r=-0.63, P<0.01), and positively with flow-mediated vasodilation (r=0.50, P<0.05) in preeclamptic women, but not in women with uncomplicated pregnancies. Similar to the patients with metabolic syndrome, we found that dysregulation of adipocytokines, such as low adiponectin levels and high levels of other adipocytokines, and excess body weight gain during pregnancy, may decrease plasma adiponectin concentrations that are associated with endothelial dysfunction in preeclamptic women.

Topics: Adipokines; Adiponectin; Body Weight; Case-Control Studies; Endothelium, Vascular; Female; Humans; Interleukin-6; Leptin; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Pre-Eclampsia; Pregnancy; Triglycerides; Vasodilation

The cause of preeclampsia remains unknown. Excessive antiangiogenic proteins have been proposed to play a pathogenic role in preeclampsia.. Our objective was to determine the differences in soluble endoglin (sEndoglin), soluble fms-like tyrosine kinase receptor-1 (sFLT1), leptin, adiponectin, and endothelin 1 concentrations between normal and preeclampsia amniotic fluid (AF). Such results may help us understand the pathophysiology of preeclampsia.. We performed a nested case-control study. Seventy-one women with preeclampsia were matched to 71 normotensive controls. The preeclamptic women were broken into two subgroups according to the association with fetal intrauterine growth restriction (IUGR). AF concentrations of sEndoglin, sFLT1, leptin, adiponectin, and endothelin 1 were measured by ELISA. Receiver-operating characteristics curve analysis was used to compare the discriminative values of these potential biomarkers. Functional network analysis was performed using MetaCore to reveal the common functions of the interacting proteins.. Increased AF concentrations of sFLT1, sEndoglin, endothelin 1, and leptin were found in women who later developed preeclampsia. sFLT1, sEndoglin, leptin, and adiponectin were significantly higher in the preeclampsia with IUGR than those without IUGR. Leptin has the largest area under the curve (0.753). Network analysis revealed that elevated amniotic proteins are involved in the inflammatory process of the human placenta.. Significant elevation of leptin can be detected in AF 2 months earlier than the appearance of symptoms; thus, it may be used as a predictive marker for preeclampsia. The increase of these antiangiogenic proteins supports the roles of inflammation and oxidative stress in pathogenesis of preeclampsia.

Topics: Adiponectin; Adult; Amniotic Fluid; Analysis of Variance; Antigens, CD; Case-Control Studies; Chi-Square Distribution; Endoglin; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Fetal Growth Retardation; Humans; Leptin; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Prospective Studies; Receptors, Cell Surface; Regression Analysis; ROC Curve; Vascular Endothelial Growth Factor Receptor-1

Normal gestation implants on a relatively hypoxic deciduas so that trophoblast deeply invades endometrium and angiogenesis seeks for oxygen supply. If implantation occurs before those hypoxic conditions occur, trophoblast invasion is defective, due to the relatively high oxygen tension in the decidual environment, laying the foundations for subsequent pre-eclampsia.

Topics: Carbon Monoxide; Female; Humans; Hyperoxia; Hypoxia; Leptin; Oxidative Stress; Pre-Eclampsia; Pregnancy; Smoking

This study was carried out to investigate changes in the plasma leptin concentrations during preeclampsia treatment and to determine whether antihypertensive treatments, aimed at decreasing leptin levels, would improve foetal outcomes.. A prospective study was undertaken in 57 pregnant women with preeclampsia (37 with mild and 20 with severe preeclampsia) and 46 normal pregnant women who were matched in maternal and gestational age and body mass index. The mild preeclampsia group was treated with alpha-methyldopa, while the severe preeclampsia group was treated with a combination of alpha-methyldopa and nifedipine.. The severe preeclampsia group had significantly lower platelet counts, higher systolic and diastolic blood pressures and elevated serum uric acid concentrations. Pre-treatment plasma leptin levels were significantly increased in the severe preeclampsia group (range 18.3-49.5) compared to the the mild preeclampsia group (range 20.7-45.4) and normal controls (range 8.6-19.2). Post-treatment plasma leptin levels in both the mild and severe preeclampsia groups (range 10.2-23.5 and 11.3-24.4, respectively) were statistically similar to those of the control group (range 9.1-20.7). Estimated foetal weight, intrauterine growth retardation and demise were statistically similar in the three study groups.. Plasma leptin concentrations were found to be elevated in women diagnosed with severe preeclampsia. However, the exact mechanism underlying the increased plasma leptin levels in preeclampsia and the functional role of leptin in the development of hypertension need to be further clarified. Leptin has a promising future as a valuable marker to identity women with a high risk for preeclampsia.

Topics: Adult; Antihypertensive Agents; Case-Control Studies; Female; Humans; Leptin; Platelet Count; Pre-Eclampsia; Pregnancy; Prospective Studies; Uric Acid; Young Adult

To determine the connection between maternal first trimester serum leptin levels and newborn weight.. The study included 37 preeclamptic women and 53 normotensive women who considered the control group. Maternal blood samples were withdrawn at 13 weeks of gestation for the measurement of leptin concentrations. Birth weights were transformed to z-scores according to maternal and obstetrical features, based on customized centiles. Non-parametric tests, student's t-test, Pearson's correlation, Spearman's correlation and linear regression analysis were performed in our analysis.. Pre-pregnancy body mass index and first trimester maternal plasma leptin levels were significantly higher among women with preeclampsia (p=0.015 and p<0.001, respectively). Birth weight z-score was negatively correlated with leptin levels (r= -0.570, p<0.001), in preeclamptic group and in control group (r= -0.477, p<0.001). The regression modelling demonstrated a significant negative association between birth weight z-scores and leptin for both groups.. Maternal first trimester serum leptin demonstrates a significant negative association with neonatal weight in preeclamptic pregnancies and to a lesser extent in normotensive pregnancies. A possible leptin's involvement in pathophysiological adaptations that define the foetal growth potential can be supported.

Topics: Adult; Birth Weight; Body Mass Index; Female; Gestational Age; Humans; Infant, Newborn; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Regression Analysis

To assess the relation between serum leptin levels and lipid profile in women with pre-eclampsia and to evaluate their atherogenic role in the pathophysiology of pre-eclampsia.. This was a comparative cross-sectional study, carried out in the Department of Physiology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre (JPMC), in collaboration with the department of Gynaecology and Obstetrics, JPMC. For this purpose 45 primigravidas with normal pregnancy and 45 primigravidas with pre-eclamptic pregnancy were selected who were in their third trimester. All the subjects were of the same maternal age, gestational age, height and weight. Serum leptin levels were determined by immunoenzymometric assay and total lipid profile was determined by enzymatic colorimetric method.. The study included 90 patients, divided into two groups of whom 45 were diagnosed as pre-eclampsia and 45 were controls. All the variables of the lipid profile of pre-eclamptic patients, were found to be significantly elevated as compared to controls. The total lipid profile was also compared to the severity of pre-eclampsia and total cholestrol was found to be significantly raised (p < 0.01) in severe pre-eclampsia when compared to mild. On correlating serum leptin with lipid profile, again total cholestrol was found to be significantly high (p < 0.05) in pre-eclamptic group compared to controls.. This study concluded that serum leptin levels during pre-eclampsia are strongly associated with total cholesterol whereas association with other variables is insignificant. With severity of pre-eclampsia when leptin level rises, total cholesterol also rises. These changes may be the result of oxidative stress and may contribute to atherogenesis and pathogenesis of pre-eclampsia.

Topics: Adolescent; Adult; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Immunoenzyme Techniques; Leptin; Lipids; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Severity of Illness Index; Young Adult

Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment.. Here we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE). DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels) that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF) signaling by soluble VEGF receptor 1 (sFlt-1) is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies.. We described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans.

Topics: Animals; Blood Pressure; Disease Models, Animal; Female; Leptin; Mice; Mice, Inbred CBA; Mice, Inbred DBA; Pravastatin; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Vascular Endothelial Growth Factor A

Adiponectin and leptin are members of the adipocytokine family. Adiponectin promotes and leptin inhibits apoptosis and both are regulators of angiogenesis. Adipocytokines and their receptors are expressed in the placenta, and in the pre-eclamptic (PE) mother the serum levels of both are higher than in healthy ones. Our aim was to study the expression of adiponectin, leptin, their receptor genes and apoptosis in severely PE and normal placentas.. The study group comprised 13 PE mothers and their 16 healthy controls. Placental biopsies were taken during cesarean section, the RNA was extracted and micro-array study was performed, followed by PCR and apoptosis studies.. The placental expression level of the leptin and adiponectin receptor 1 genes was significantly higher in PE mothers than in controls. No significant changes were observed in the levels of the adiponectin, adiponectin receptor 2 and Leptin receptor genes. The expression of the Adiponectin gene was low. The rate of apoptosis was higher in the PE placentas.. The activity of placental adipocytokines and their receptor genes in severe PE may suggest an important role in placental angiogenesis. Placental apoptosis induced by adiponectin could be mediated via the ADIPOR1-receptor.

Topics: Adiponectin; Adult; Apoptosis; Case-Control Studies; Female; Fetal Growth Retardation; Humans; Leptin; Oligonucleotide Array Sequence Analysis; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Receptors, Adiponectin; Receptors, Leptin

We investigated the global placental gene expression profile in severe preeclampsia. Twenty-one women were randomly selected from 50 participants with uncomplicated pregnancies to match 21 patients with severe preeclampsia. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate the gene expression profile. After RNA isolation, five preeclamptic placentas were excluded due to poor RNA quality. The series composed of 37 hybridizations in a one-channel detection system of chemiluminescence emitted by the microarrays. An empirical Bayes analysis was applied to find differentially expressed genes. In preeclamptic placentas 213 genes were significantly (fold-change>or=2 and p

Topics: Adult; Angiogenesis Inducing Agents; Chorionic Gonadotropin; Down-Regulation; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Leptin; Metalloproteases; Oligonucleotide Array Sequence Analysis; Parity; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Notch; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation

The adipokines adiponectin and leptin may contribute to preeclampsia; however, the reports are conflicting. We explored the issue further.. We studied 25 pregnant women with normal pregnancy in first, 25 in second, and 30 in third trimesters, 15 healthy nonpregnant women, and 32 women with preeclampsia. We used enzyme-linked immunosorbent assay to measure human plasma adiponectin (ng/mL) and leptin (ng/mL) concentrations. We also investigated adiponectin and leptin expression by quantitative messenger RNA in fat, decidua, and placenta tissues in a second study.. Prepregnancy body mass index was not different in preeclamptic and nonpreeclamptic women. Plasma adiponectin concentrations increased throughout normal pregnancy, compared to nonpregnant women. The values increased in every trimester but were invariably lower in women with preeclampsia. Adiponectin nonetheless correlated inversely with prepregnancy body mass index. Such correlations were not found in women with preeclampsia. Plasma leptin in contrast decreased during pregnancy in every trimester. Leptin values were much higher in preeclamptic than in nonpreeclamptic women. Leptin expression was increased in the uteroplacental unit and in fat tissue of preeclamptic, compared to nonpreeclamptic women, while no differences in adiponectin expression were found.. Adiponectin increases in normal pregnancy but remains correlated with prepregnancy body mass index. Plasma leptin decreases in normal pregnancy. In preeclamptic women, the normal adipokine responses are perturbed and this could be of pathophysiological significance.

Topics: Adipokines; Adiponectin; Adult; Biomarkers; Female; Humans; Infant, Newborn; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Uterus

To explore the role of endothelin-1 (ET-1) and leptin in intrauterine growth restriction (IUGR) among preeclamptic and non-pre-eclamptic women.. Forty three patients with a pregnancy complicated by IUGR, 23 cases with severe pre-eclampsia and 20 cases of non-pre-eclamptic were enrolled. Control group comprised 15 cases with uncomplicated pregnancy. Blood samples from umbilical artery and maternal venous blood were collected at the time of delivery for analysis of ET-1 and leptin levels. Mode of delivery, birth weight and Apgar score were also recorded.. The mean maternal and fetal ET-1 level was significantly higher in pregnancies complicated by IUGR than in control group. The mean maternal leptin level was significantly higher in pre-eclamptic patients when compared to non-preeclamptic and control groups. Mean fetal leptin level was significantly lower in patients compared to control; however, when fetal leptin corrected to fetal weight, it was insignificantly different in the both groups. E-mail: m. alhaggar@yahoo.co.uk.. Maternal plasma ET-1 and leptin correlate with the degree of fetal growth restriction originating from deterioration of placental function. Maternal plasma leptin and ET-1 levels may reflect deterioration in fetal growth.

Topics: Adult; Analysis of Variance; Biomarkers; Birth Weight; Case-Control Studies; Chi-Square Distribution; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Leptin; Linear Models; Maternal Age; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Prenatal Care; Probability; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Ultrasonography, Prenatal; Young Adult

To evaluate the role of the adipokines, visfatin and leptin in the pathophysiology of pre-eclampsia and how their concentrations correlate with the severity of the disease and abnormal Doppler velocimetry.. A cross-sectional study was carried out in 72 pregnant women (30 patients with mild pre-eclampsia, 20 patients with severe pre-eclampsia and 22 healthy normotensive pregnant women) during the third trimester of pregnancy. The maternal levels of plasma visfatin and serum leptin were determined in all cases by enzyme immunoassay and enzyme-linked immunosorbent assay, respectively. The uterine artery and umbilical artery RI were determined by Doppler analysis in all cases.. Plasma visfatin levels and serum leptin levels were higher in patients with pre-eclampsia than in the normotensive pregnant women. Six patients with mild pre-eclampsia and five patients with severe pre-eclampsia had abnormal Doppler velocimetry. Visfatin and leptin levels of pre-eclamptic patients with abnormal Doppler velocimetry were significantly higher than they were in those with normal Doppler velocimetry. Serum leptin levels were positively correlated with plasma visfatin level in cases of pre-eclampsia.. These findings suggest that increased maternal levels of leptin and visfatin may be involved in the pathogenesis of pre-eclampsia, and measurement of these adipokines may be useful in assessment of the severity of disease.

Topics: Adult; Blood Flow Velocity; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Nicotinamide Phosphoribosyltransferase; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Severity of Illness Index; Ultrasonography, Doppler; Ultrasonography, Prenatal; Up-Regulation; Young Adult

Leptin plays an important role in energy homeostasis. There is polymorphism on the leptin (LEP) gene. Our aim was to compare the tetranucleotide repeat (TTTC)(n) polymorphism in the 3'-flanking region in the LEP gene on DNA samples from patients with pre-eclampsia (PE), hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome and healthy pregnant controls.. Blood samples were collected from healthy pregnant women (n=88), patients with PE (n=79) and HELLP (n=77) syndrome. Fluorescent PCR and DNA fragment analysis was performed from the isolated DNA for the detection of (TTTC) repeats. The electrophoretograms were evaluated and patients were assigned to two groups; class I low (<190 bp) or class II high (> or =190 bp) PCR fragments.. We observed similar distributions of the class I and class II (TTTC) alleles in the groups studied (class I allele: healthy pregnant 58.5%; severe pre-eclamptic 58.3%; HELLP syndrome 52.6%). We detected a higher frequency of the II/II genotype in HELLP syndrome patients (32.4%) compared to healthy controls (22.7%). However, the difference was not statistically significant.. In an ethnically homogenous population, the LEP gene (TTTC) microsatellite polymorphism in the 3'-flanking region does not show a significant difference in the allele and genotype distribution in healthy pregnant, pre-eclamptic and HELLP syndrome patients. Furthermore, we recommend a new classification of the class I and class II alleles based on the distribution of the (TTTC) microsatellites.

Topics: 3' Flanking Region; Adult; Alleles; Female; Genotype; HELLP Syndrome; Humans; Leptin; Microsatellite Repeats; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy

Leptin is a polypeptide hormone (167 amino acids, molecular weight of about 16kDa), synthesized mainly in white adipose tissue. The hormone plays an important role in regulation of hunger and satiety processes, in metabolism of carbohydrates and fats, development of cardio-vascular diseases and obesity. The occurrence of the increased level of leptin in pregnant women with hypertension, especially in women with preeclampsia, has also been brought to our attention. In recent years it has been suggested that the presence of different variants of leptin and leptin receptor genes may modify the leptin level in serum, and, in this way, influence an increased risk of obstetric complications, such as preeclampsia or eclampsia.. We have analyzed a group of 103 hypertensive pregnant women--61 women with gestational hypertension (GH) and 42 women with preeclampsia (PE). The control group consisted of 113 healthy pregnant women who have been investigated. Gestational hypertension and preeclampsia were recognized with the help of and assessed according to the ACOG criteria. The (-2548G/A) polymorphism was determined using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP).. In our study, a higher frequency of mutated AA genotype in GH group and PE groups (21.31% and 21.43% respectively vs. 16.81% in the controls) and the overrepresentation of mutated A allele in both analyzed groups (47.54% and 45.24% respectively vs. 41.59% in the controls) have been observed, without statistically significant differences.. The overrepresentation of AA genotypes and higher frequency of mutated A allele of (-2548G/A) polymorphism of leptin gene in GH and PE groups might indicate its possible contribution in gestational hypertension and preeclampsia.

Topics: Adult; Case-Control Studies; DNA Mutational Analysis; Female; Genotype; Humans; Hypertension; Leptin; Point Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

Preeclampsia, a common complication of pregnancy, is associated with alteration in the concentration of leptin in maternal blood. The action of leptin is antagonistic to that of ghrelin. Here, we compared the levels of leptin and ghrelin in maternal serum and in arterial and venous cord blood between healthy pregnant women and those suffering from mild and severe preeclampsia. The levels of leptin in maternal and newborn's blood were elevated in both mild and severe preeclamptic patients (p < 0.05). Moreover, serum ghrelin levels were negatively correlated with blood pressure and leptin/ghrelin ratio was decreased in preeclampsia (p < 0.05). We concluded that increased production of ghrelin may represent a compensatory hypotensive mechanism in preeclamptic women.

Topics: Adaptation, Physiological; Adult; Arteries; Blood Pressure; Female; Fetal Blood; Ghrelin; Humans; Infant, Newborn; Leptin; Pre-Eclampsia; Pregnancy; Veins

We investigated whether the increase of leptin expression in preeclamptic placentas is additionally influenced by soluble maternal factors under hypoxic and nonhypoxic conditions.. Term trophoblast cells were isolated and stimulated with sera from preeclamptic women under normoxic or hypoxic conditions. Levels of leptin mRNA and protein were evaluated by real-time RT-PCR or ELISA and Western blot analysis.. Leptin concentrations were increased in the serum of patients with preeclampsia and gestational diabetes. Hypoxia, insulin, and dexamethasone induced leptin expression in trophoblast cells. The incubation with sera from preeclamptic women led to a small, though, significant, increase of leptin gene expression. The effect of preeclamptic serum on leptin gene expression in trophoblast cells was lost under hypoxia. The serum of women with gestational diabetes did not increase leptin expression neither in normoxic nor hypoxic primary trophoblast cells.. Our results can not exclude a soluble maternal factor in the serum of women with preeclampsia accounting for increased leptin expression in placental tissue in addition to hypoxia. However, an important biological role of this small increase in nonhypoxic conditions does not seem very likely.

Topics: Adult; Case-Control Studies; Cells, Cultured; Diabetes, Gestational; Female; Humans; Hypoxia; Leptin; Pre-Eclampsia; Pregnancy; Trophoblasts

The pathophysiology of pre-eclampsia, one of the leading causes of maternal mortality worldwide, still remains unclear. Recently, it has been suggested that impaired regulation of complex interactions among various adipokines plays an important role in the development of pre-eclampsia. The aim of this study was to investigate whether the two common polymorphisms of the leptin (LEP) and adiponectin (APM1) genes are associated with the development of pre-eclampsia and its related traits (gestational hypertension, proteinuria and various measures of reduced fetal growth ) in the Czech pre-eclamptic population.. The case-control study comprised a total of 123 pre-eclamptic women and 150 healthy controls of similar age and parity distribution. They were genotyped for the LEP -2548G/A (5'-untranslated region) and APM1 T94G (exon 2) polymorphisms using polymerase chain reaction.. The allele frequency of the LEP -2548G polymorphism was 0.541 in the pre-eclamptic group versus 0.583 in the control group (P=0.578); the frequency of the APM1 94G polymorphism was 0.073 and 0.079 (P=0.628), respectively. No significant associations were detected between either of the two single nucleotide polymorphisms or any of the parameter biomarkers related to pre-eclampsia, such as gestational hypertension or proteinuria. However, the APM1 T94G polymorphism was significantly associated with a low birth weight in pre-eclamptic pregnancies, with mothers carrying the T-allele having an almost three-fold increase in the likelihood of giving birth to a child with a low birth weight for its gestational age (odds ratio, 2.7; 95% confidence interval, 0.18-5.9; P=0.004).. The APM1 T94G and LEP -2548G/A polymorphisms do not seem to be major genetic determinants of susceptibility to pre-eclampsia in the Czech Caucasian population. However, evidence has been provided for possible APM1 T94G involvement in controlling the birth weight of children from pre-eclamptic pregnancies, thus supporting the hypothesis of T94G involvement in controlling the birth weight of newborns.

Topics: Adiponectin; Adult; Case-Control Studies; Cohort Studies; Female; Genetic Predisposition to Disease; Humans; Infant, Newborn; Leptin; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy

Adiponectin and leptin, two adipose-tissue-derived proteins, have been reported to be elevated in women with established PE (pre-eclampsia). The aim of the present study was to investigate whether alterations in adiponectin and leptin levels predate the development of PE and FGR (fetal growth restriction) in women at increased risk of these complications, as assessed by Doppler examination of the uterine arteries during the second trimester of pregnancy. We also sought to investigate the circulating levels of adiponectin and leptin in women with established severe early-onset FGR. The study included three groups of pregnant women at 23-25 weeks: Group A (n=44) with normal uterine artery Doppler waveforms, Group B (n=49) with abnormal Doppler waveforms and normal fetal growth at the time of the examination, and Group C (n=15) with established severe FGR and abnormal Doppler waveforms. All women had plasma adiponectin and leptin measured by sensitive immunoassays. In Group B, 19 women had a normal outcome, 17 delivered infants with FGR and 13 developed PE. The women who developed PE delivered smaller babies earlier than women with a normal outcome (P<0.001). There were no significant differences in adiponectin levels between any of the groups (overall P=0.3). Leptin concentrations, expressed as MoM (multiples of the median) of Group A, were higher in women in Group C, i.e. established severe FGR at 2.5 (1.2-2.7) MoMs (overall P<0.001), compared with all of the other groups and subgroups. In conclusion, we found that, in pregnancies complicated by severe early-onset FGR, the maternal plasma concentration of leptin is twice as high as in normal pregnancies. However, the second trimester levels of maternal plasma adiponectin and leptin in pregnancies that subsequently develop PE and/or FGR are not significantly different from normal and, consequently, it is unlikely that these markers will be useful as predictors of these pregnancy complications.

Topics: Adiponectin; Adult; Biomarkers; Female; Fetal Growth Retardation; Humans; Leptin; Placentation; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Retrospective Studies; Ultrasonography, Doppler, Color; Uterus

The human placenta is prerequisite for the development of gestational hypertensive diseases like early-onset preeclampsia (PE) and Hemolysis, Elevated Liver enzymes and Low platelets (HELLP) syndrome. Both syndromes are associated with extensive maternal and perinatal mortality, and morbidity with life long consequences. We aimed to investigate differences in gene expression between placental tissue obtained from normotensive pregnant women and women with PE and HELLP syndrome. Firstly, comparison of Serial Analysis of Gene Expression profiles of 28 weeks' control placenta (available after idiopathic premature delivery) to a HELLP/PE placenta matched for gestational age identified 404 differentially expressed transcripts. Secondly, using sqPCR, the expression levels of 37 of these transcripts were analyzed in placentas of 36 pregnant women, 22 with preeclampsia and HELLP syndrome. Thirdly, nearest centroid classification determined the HELLP specific molecular signature consisting of the upregulated expression of genes encoding the vascular endothelial growth factor receptor (FLT1), leptin (LEP), pappalysin 2 (PAPPA2), and WW domain containing transcription regulator 1 (WWTR1) combined with down regulated expression of the genes encoding cadherin-associated protein (CTNNAL), glutathione S-transferase pi (GSTP1) and calgranulin A (S100A8). This set discriminates HELLP placenta from control and PE placenta with a 24% misclassification rate (95% CI 8.3-41.9%), independent from known risk factors like parity and ethnicity. The transcripts involved correspond to diverse molecular pathways, exemplifying the multigenic molecular basis of the disorder. This distinct placental molecular signature suggests that HELLP is not a PE variant but a separate disease entity. Our data may prove fundamental for the further molecular analysis of PE and HELLP syndrome.

Topics: Acyltransferases; Algorithms; alpha Catenin; Calgranulin A; Case-Control Studies; Female; Gene Expression Profiling; Gene Library; Glutathione S-Transferase pi; HELLP Syndrome; Humans; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy-Associated Plasma Protein-A; RNA, Messenger; Transcription Factors; Vascular Endothelial Growth Factor Receptor-1

Leptin, one of adipocytokines, plays a wide range of important roles in reproductive biology. We have previously reported that low hypo-adiponectinemia might be involved in the pathophysiology of overweight preeclampsia (PE) patients. Moreover, recent reports have underscored the importance of circulating angiogenic factors in the pathophysiology of PE. Here, we examined whether leptin in conjunction with adiponectin and/or angiogenic factors plays some role in the pathophysiology of PE. We performed a cross-sectional study in 34 PE patients and normal pregnancies matched for gestational age and body mass index as controls. We measured serum concentrations of leptin, adiponectin, the angiogenic factors vascular endothelial growth factor (VEGF), placental growth factor, and the soluble VEGF receptors sFlt-1 and sFlk-1. We observed that leptin levels in PE patients were significantly higher compared with those in controls, but did not observe significant differences between normal- and overweight patients in both groups. We also showed a significant negative correlation between leptin and adiponectin in controls, but not in PE patients. There was a significant correlation between leptin and sFlt-1 in PE patients, while there were significant differences of body mass index, mean blood pressure and proteinuria between high and low leptin/sFlt-1 ratio group in PE patients. Moreover, there was a significant difference of leptin level between IUGR and normal growth group in PE patients. These results suggest that the circulating increased leptin might be derived mainly from the placenta and regulated by the placental hypoxic condition, whereas adiponectin might be derived mainly from adipose tissue; and that leptin might play some role through insulin resistance, autonomic activation, or direct effect on endothelium with other angiogenic factors in pathophysiology of PE compared with the exaggerated release of adiponectin from adipose tissue.

Topics: Adiponectin; Adult; Angiogenesis Inducing Agents; Case-Control Studies; Female; Humans; Infant, Newborn; Insulin Resistance; Leptin; Membrane Proteins; Overweight; Pre-Eclampsia; Pregnancy; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2

Parallel investigation, in a matched case-control study, of the association of different first-trimester markers with the risk of subsequent pre-eclampsia (PE).. The levels of different first trimester serum markers and fetal nuchal translucency thickness were compared between 52 cases of PE and 104 control women by non-parametric two-group comparisons and by calculating matched odds ratios.. In univariable analysis increased concentrations of inhibin A and activin A were associated with subsequent PE (p < 0.02). Multivariable conditional logistic regression models revealed an association between increased risk of PE and increased inhibin A and translucency thickness and respectively reduced pregnancy-associated plasma protein A (PAPP-A) and placental lactogen . However, these associations varied with the gestational age at sample collection. For blood samples taken in pregnancy weeks 12 and 13 only, increased levels of activin A, inhibin A and nuchal translucency thickness, and lower levels of placenta growth factor and PAPP-A were associated with an increased risk of PE.. Members of the inhibin family and to some extent PAPP-A and placental growth factor are superior to other serum markers, and the predictive value of these depends on the gestational age at blood sampling. The availability of a single, early pregnancy 'miracle' serum marker for PE risk assessment seems unlikely in the near future.

Topics: Adult; Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Humans; Inhibins; Interleukin-8; Leptin; Logistic Models; Nuchal Translucency Measurement; Placenta; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Proteins; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Retrospective Studies

Insulin resistance syndrome has been observed in women with hypertensive disease of pregnancy, but few studies evaluated the presence of the syndrome a few years after delivery. The objective of this study was to evaluate the presence of insulin resistance and its metabolic alterations in these women compared with those who had a normal pregnancy. We performed an observational study in 168 women with previous hypertensive disease of pregnancy and 168 control subjects with normal pregnancy contacted, on average, 7.8 years after their first delivery (mean age: 34.8 years). Complete blood lipid profile, insulin, glucose, homocysteine, adipokins, and markers of inflammation were measured. Also, an oral glucose tolerance test was performed in 146 case and 135 control subjects. Case subjects were more overweight compared with control subjects. We found significantly lower high-density lipoprotein cholesterol and adiponectin levels and higher apolipoprotein (apo) apoB/apoA1 ratio, homocysteine, leptin, and insulin levels among case subjects compared with control subjects (P

Topics: Adiponectin; Adult; Apolipoprotein A-I; Apolipoproteins B; Biomarkers; Body Mass Index; Cholesterol, HDL; Female; Glucose Tolerance Test; Humans; Hypertension, Pregnancy-Induced; Insulin; Insulin Resistance; Leptin; Medical Records; Overweight; Pre-Eclampsia; Pregnancy; Time Factors

Recent reports have demonstrated that soluble endoglin (sEng), an antiangiogenic protein thought to impair TGF-beta binding to receptors, and soluble vascular endothelial growth factor receptor (sVEGFR)-1 play important roles in the pathophysiology of preeclampsia (PE). Moreover, insulin resistance, which is greatly influenced by adipocytokines, characterizes PE.. We examined possible links between sEng, VEGF, sVEGFR, and adipocytokines in the pathophysiology of PE.. We performed a cross-sectional study in 30 PE patients and controls matched for gestational age and body mass index. Blood samples were collected soon after disease onset. We measured serum concentrations of leptin, adiponectin, sEng, VEGF, placental growth factor (PlGF), and sVEGFR [soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble fetal liver kinase 1 (sFlk-1)], and examined the placental protein content of sEng and sFlt-1.. sEng concentrations in PE patients (60.9 +/- 28.8 ng/ml) were significantly higher than those in controls (11.2 +/- 4.4 ng/ml). There was a significant correlation between sEng and sFlt-1 or PlGF. Moreover, there were significant differences in mean blood pressure between the high and low sEng groups, and in proteinuria between the high and low sFlt-1 groups, and significant differences in placental sEng and sFlt-1 contents between patients with and without severe hypertension or proteinuria. sEng was also correlated positively with adiponectin levels and negatively with the leptin to adiponectin ratio.. Along with sFlt-1 and PlGF, sEng might play a role in the pathophysiology of PE, especially in elevating blood pressure, while the association with hypoadiponectinemia and the high leptin to adiponectin ratio in pregnancy seem to be risk factors for PE.

Topics: Adiponectin; Adult; Antigens, CD; Blood Pressure; Endoglin; Female; Humans; Leptin; Placenta; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Receptors, Cell Surface; Risk Factors; Severity of Illness Index; Solubility; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2

To identify parameters that may assist clinicians in predicting which women will develop preeclampsia (PE) after initially presenting with gestational hypertension (GH).. 118 women were recruited to the study with GH or PE. They were divided into three groups based on their diagnosis at delivery- (1) GH, (2) PE from the time of presentation, (3) those with an initial diagnosis of GH who progressed to PE. Women underwent 24 hour ambulatory blood pressure monitoring (ABPM) and had serum estrogen, progesterone, beta-HCG, leptin and adiponectin measured as possible predictors of transformation of GH to PE.. Women who presented with GH, and progressed to PE, presented four weeks earlier (33 vs 37 weeks, p < 0.001) than those who did not progress. Women with PE, either as their initial diagnosis or after progression from GH, were delivered earlier (p < 0.001) and had more small for gestational age (SGA) babies than women with GH at delivery (p < 0.05). Those who developed PE after presenting with GH generally had higher blood pressures than those who remained as GH, significant for awake and 24 hour systolic blood pressures (p < 0.05). beta-HCG, estrogen, progesterone or leptin values were similar across the groups. Adiponectin was higher in women with established PE at presentation compared to women with GH (p = 0.02) but adiponectin failed to discriminate those women with an initial diagnosis of GH who progressed to PE.. 24 hr ABPM may provide a non-invasive method of identifying this 'at risk' GH population, particularly in the case of early presentation.

Topics: Adiponectin; Adult; Blood Pressure Monitoring, Ambulatory; Disease Progression; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Sensitivity and Specificity

Leptin concentrations were measured in African American women in order to assess leptin's role in the increased frequency and severity of preeclampsia. In addition, leptin concentrations were measured in women who delivered small-for-gestational-age (SGA) infants. A case-control study of African American and Caucasian women with normal pregnancies, preeclampsia, or SGA infants was done. Plasma leptin was quantitated by radio-immunoassay. The previously recognized pattern of increased leptin concentrations in preeclampsia was replicated. Leptin concentrations did not differ by race in any diagnostic category, and concentrations in women with SGA infants were not higher than those in healthy women. Differences in the frequency and severity of preeclampsia in African Americans cannot be explained by higher leptin concentrations.

Topics: Adult; Black or African American; Body Mass Index; Case-Control Studies; Female; Humans; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Pre-Eclampsia; Pregnancy; White People

Despite progress in immunobiology, pre-eclampsia (PE) remains one of the most common reasons for women to die during pregnancy. The widespread pathophysiological mechanisms are endothelial dysfunction, oxidative stress and inflammation. The aim of this study was to assess the alteration in the levels of leptin, interleukin (IL)-10 and inflammatory cytokines [tumour necrosis factor (TNF)-alpha, IL-6 & IL-8] in pre-eclamptic (severe and mild), healthy pregnant and non-pregnant women and correlate these parameters with disease severity.. The levels of leptin, IL-10 and inflammatory cytokines were measured by high sensitivity enzyme-linked immunoabsorbant assay. The study subjects were 54 pre-eclamptic women (ten severe and 45 milder), compared by age matched 50 healthy pregnant and 27 non-pregnant women. Kruskal-Wallis non-parametric analyses of variance followed by Mann-Whitney U-test were used for statistical analysis.. The levels of leptin, TNF-alpha, IL-6 & IL-8 in pre-eclamptic subjects were increased significantly when compared with the healthy control pregnant and non-pregnant (P < 0.000). The concentration of IL-10 has shown different pattern as its level decreased significantly (0.001) in pre-eclamptic women (overall) in comparison with control subjects (pregnant & non-pregnant). A combination of 80% or higher sensitivity and specificity was seen in the parameters analysed, except IL-8 and IL-10.. Our findings suggest a relationship among TNF-alpha, IL-6, IL-8, IL-10 and leptin and indicate that altered levels of above markers in PE might be used as markers of pro-inflammation/anti-inflammation and endothelial dysfunction in pre-eclamptic pregnancies. These results also advocate the abnormal leptin and cytokine responses in mother, which might be involved in the pathogenesis of PE.

Topics: Cytokines; Female; Humans; Immunoassay; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Pre-Eclampsia; Pregnancy; Tumor Necrosis Factor-alpha

To clarify the role of adipocytokine, adiponectin, and leptin in the pathogenesis of pre-eclampsia (PE) and determine the relationships between plasma adiponectin and leptin levels.. A total of 73 women in the third trimester of pregnancy were recruited, 53 women with PE (study patients) and 20 age- and BMI-matched normotensive women (healthy controls). They were divided into 3 groups: the 20 normotensive pregnant women (group 1); 32 women with mild pre-eclampsia (group 2); and 21 women with severe pre-eclampsia (group 3). The plasma levels of adiponectin and leptin are measured simultaneously and their correlation and balance were evaluated by enzyme-linked immunosorbent assay.. Compared with controls, levels of adiponectin were significantly lower in women with mild or severe PE (P<0.01 for both groups) whereas levels of leptin were significantly higher in women with mild or severe PE (P<0.05 and P<0.01, respectively). There was a negative correlation between plasma levels of adiponectin and leptin in pre-eclamptic women (r=-0.76, P<0.01). Moreover, the adiponectin level to leptin level ratio was significantly lower in pre-eclamptic women than that in healthy controls (P<0.01). In the pre-eclamptic women serum levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol were significantly increased (P<0.01 for all), while high-density lipoprotein cholesterol was significantly decreased compared to levels in normotensive pregnant women (P<0.01).. These findings suggest that there is an imbalance between adiponectin and leptin in the plasma of pre-eclamptic women. Reduced adiponectin and elevated leptin levels may be involved in the pathogenesis of PE and associated with the development of severe disease.

Topics: Adiponectin; Adult; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

Leptin is a satiety hormone secreted from the adipose tissue and human placenta. We previously demonstrated that severe preeclampsia up-regulated leptin mRNA expression in the placenta and elevated maternal plasma leptin concentrations. Preeclampsia is frequently related to generation of small for gestational age (SGA) infant especially in cases with severe preeclampsia. However, it is still controversial whether the increase in maternal plasma leptin levels is associated with fetal growth restriction without complication of preeclampsia. Therefore, the aim of the present study was to explore the relationship between maternal plasma leptin levels and fetal growth in non-preeclamptic (n = 98) and preeclamptic (n = 40) women. In non-preeclamptic pregnant women, plasma leptin levels in SGA group (n = 11) were significantly higher than those in appropriate for gestational age (AGA) group (n = 87, P<0.05). In pregnant women with preeclampsia, likewise, plasma leptin levels in SGA group (n = 15) were significantly higher than those in AGA group (n = 25, P<0.05). In multiple linear regression analysis, maternal BMI, mean arterial blood pressure and Delta SD of neonatal body weight were significant factors for determining maternal plasma leptin levels in all population studied. Maternal BMI and Delta SD of neonatal body weight showed positive correlation with maternal plasma leptin levels when analysis was performed in non-preeclamptic subjects alone. In conclusion, maternal plasma leptin levels reflect, at least partly, deterioration in fetal growth.

Topics: Adult; Blood Pressure; Body Mass Index; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Linear Models; Pre-Eclampsia; Pregnancy

To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex.. Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex.. Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004).. Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.

Topics: Amniotic Fluid; Female; Gestational Age; Humans; Leptin; Male; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Risk Factors

Growing evidence suggests that concentration of the adipocytokines leptin and adiponectin may be affected by risk of hypertension during pregnancy. Leptin and leptin receptor gene expression has been studied in placentas obtained from pre-eclamptic patients, but not in those with chronic high blood pressure (CHBP). Adiponectin receptors remain unstudied in placentas obtained from hypertensive patients.. Therefore, we investigated relative mRNA expression of selected adipocytokine genes (leptin, leptin receptors (LEPRA, LEPRB, LEPRC, LEPRD) and adiponectin receptors (ADIPOR1, ADIPOR2)) in placental tissues from women with pre-eclampsia (n = 6) or CHBP (n = 8). Placentas from 28 normotensive patients were analyzed as controls. mRNA extracted from biopsies taken from the maternal and fetal sides of the placenta was investigated using real-time polymerase chain reaction.. Compared with controls, significant increases in leptin mRNA expression were seen in placentas from pre-eclamptic patients on the maternal (p = 0.01) and fetal (p = 0.02) sides, and in placentas from CHBP mothers on the fetal side (p = 0.001). Maternal-side tissue from CHBP patients was not significantly different from that of controls (p = 0.08), but this might be due to the small sample size. No significant differences were seen in mRNA expression for most of the adipocytokine receptors tested for hypertensive cases compared with controls. However, there was a decrease in LEPRC (pre-eclamptic, maternal side, p = 0.03) and LEPRD (pre-eclamptic, maternal side, p = 0.01; CHBP, fetal side, p = 0.009) in case-control analysis.. This pilot study shows that increases seen in leptin expression in placentas from hypertensive mothers might be a consequence of defects in placentation associated with this disease, and motivates further region-specific adipocytokine gene expression analysis across this organ.

Topics: Adult; Chronic Disease; Cytokines; Female; Gene Expression; Humans; Hypertension; Leptin; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Receptors, Adiponectin; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger

Leptin, an adipocyte hormone involved in energy homeostasis, is important in reproduction and pregnancy. Questions yet to be addressed include the source of higher leptin during pregnancy and its relationship to pregnancy outcome and fetal growth. The objective of this study was to investigate the relationship between placental leptin gene expression, placental leptin protein concentration and maternal plasma leptin concentration among control pregnant women, women with pre-eclampsia and women with growth-restricted infants. We also investigated the relationship between placental leptin expression and the placental expression of enzymes involved in cellular lipid balance: fatty acid translocase (CD36), carnitine palmitoyltransferase I (CPT-1B) and lipoprotein lipase (LPL). Placental leptin expression, placental protein and maternal plasma concentration were higher in pre-eclampsia than in controls but not in women with growth-restricted infants. Placental leptin expression and placental protein were higher in the preterm pre-eclamptic subjects, whereas maternal leptin was higher in the term pre-eclamptic subjects. The placental gene expression of CD36, CPT-1B and LPL were not different among the groups. This study suggests that despite similar failed placental bed vascular remodelling in pre-eclampsia and intrauterine growth restriction (IUGR), leptin gene expression is higher only in preterm pre-eclampsia.

Topics: Adult; Carnitine O-Palmitoyltransferase; CD36 Antigens; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Premature; Leptin; Lipoprotein Lipase; Maternal-Fetal Exchange; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Leptin; Retrospective Studies; RNA, Messenger

To delineate the changes in serum levels of adiponectin, leptin and soluble leptin receptor, and in the free leptin index in women with pre-eclampsia.. Blood samples were collected from 38 pregnant women with pre-eclampsia and 42 normotensive pregnant women as controls. Serum concentrations of adiponectin, leptin and soluble leptin receptor were determined by enzyme-link immunosorbent assay and the free leptin index was calculated as the ratio of serum leptin to soluble leptin receptor for each sample.. No significant differences were observed between the groups regarding maternal age, gestational age and body mass index. Women with pre-eclampsia had significantly higher levels of serum adiponectin and leptin, and a higher free leptin index than controls (P<0.01, P<0.001 and P<0.001, respectively). There were no significant differences between the two groups in serum levels of soluble leptin receptor (P>0.05).. The study demonstrated elevated serum levels of adiponectin and leptin as well as a higher free leptin index in women with pre-eclampsia, suggesting these as important factors contributing to this complication of pregnancy.

Topics: Adiponectin; Adult; Case-Control Studies; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Receptors, Cell Surface; Receptors, Leptin

Few investigators have simultaneously evaluated leptin, soluble leptin receptor (SLR) and leptin gene polymorphisms in preeclampsia cases and controls. We examined these three biomolecular markers in 40 preeclampsia cases and 39 controls. Plasma leptin and SLR concentrations were determined using immunoassays. Genotype for the tetranucleotide repeat (TTTC)(n), polymorphism in the 3 -flanking region of the leptin gene was determined using PCR. Alleles of the polymorphism were characterized by size distributions [short repeats (class I); and long repeats (class II)]. Logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI). Leptin concentrations were higher in our cases than in the controls (53.1 4.7 vs. 17.7+/-2.4 ng/ml, p<0.05). SLR concentrations were slightly lower in our patients than in the controls (25.7+/-1.9 vs. 29.1+/-1.1 ng/ml, p>0.05). Elevated leptin (? 14.5 ng/ml) was associated with a 3.8-fold (CI 1.0-14.4) increased risk; whereas low SLR (< 28.5 ng/ml) was associated with a 6.3-fold (CI 1.7-23.2) increased risk of preeclampsia. The I/II genotype was associated with a 3.8-fold increased risk of preeclampsia (OR=3.8; 95 % CI 0.8-18.0); and the II/II genotype was not observed among our cases (0 % vs. 33 % p<0.001). Larger studies would be needed to confirm and further clarify the relations between functional variants in the leptin gene and preeclampsia risk.

Topics: Adult; Case-Control Studies; Confidence Intervals; Female; Genetic Markers; Genotype; Humans; Leptin; Odds Ratio; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy; Receptors, Cell Surface; Receptors, Leptin; Risk Factors

Insulin resistance increases during the normal course of pregnancy, and is considered an important cause of complications including gestational diabetes mellitus, pregnancy-induced hypertension and preeclampsia (PE). Adiponectin, an adipocyte-specific plasma protein, is thought to enhance insulin sensitivity; another adipocytokine, leptin, also is thought to promote insulin sensitivity. We determined peripheral blood concentrations of adiponectin and leptin in 40 healthy nonpregnant women with a body mass index (BMI)<25, 40 healthy pregnant women with prepregnancy BMI<25, and 15 PE patients with prepregnancy BMI<25. Serum adiponectin concentrations were lower in the healthy pregnant group than in the nonpregnant group (9.40+/-4.43 versus 13.15+/-6.69 microg/mL, p<0.01), but difference disappeared after correction for haematocrit. Serum leptin concentrations were high in the normal pregnant group after correction for haematocrit (10.08+/-6.58 versus 6.24+/-3.61 ng/mL, p<0.05). Corrected after haematocrit, serum adiponectin in PE patients was higher than healthy pregnant women at 28 to 40 gestational weeks (17.46+/-11.81 versus 9.33+/-4.47 microg/mL, p<0.01). Leptin in PE was higher than in the normal pregnant group (21.15+/-19.89 versus 11.77+/-6.25 ng/mL, p<0.05), also after correction for haematocrit. These results suggested a metabolic shift in normal pregnant women and PE patients mediated through adipocytokines.

Topics: Adipocytes; Adiponectin; Adult; Biomarkers; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Pre-Eclampsia; Pregnancy

To investigate the changes in enzyme activities of erythrocyte superoxide dismutase (SOD), catalase, and placental glutathione peroxidase (GSH-Px), and analyze the levels of serum malondialdehyde (MDA), copper (Cu), zinc (Zn), selenium (Se), leptin and placental MDA and glutathione (GSH).. Cross-sectional prospective study consisting of 32 preeclamptic (PE) pregnant, 25 non-pregnant (NP) women, 28 healthy pregnant (HP) women. Levels of lipid peroxides in serum and placenta, and activities of SOD, catalase in erythrocyte and placental GSH level, placental GSH-Px activity were measured by spectrophotometric methods. Serum levels of Cu, Zn, Se measured by atomic absorption spectrophotometry. Serum levels of leptin was measured by enzyme immunoassay by using the Cayman chemical kit. One-way analysis of variance and post hoc Tukey-HSD test and Pearson correlation test were used for the statistical analyses.. Serum levels of MDA, Cu, Leptin were markedly higher (P < 0.001); and serum level of Se was markedly lower (P < 0.001) in PE women compared with HP women and NP women. Also, placental MDA level was higher (P < 0.001) and placental GSH-Px activity was lower in PE women compared with HP women. In preeclamptic women erythrocyte catalase activity was markedly increased (P < 0.001), while erythrocyte SOD activity was markedly decreased (P < 0.001) compared to HP women and NP women. Placental GSH level was decreased compared to HP women (P < 0.001). Serum level of Zn was markedly decreased compared to NP women (P < 0.001) but no significant difference was observed in PE pregnant when compared with HP women (P > 0.05). Placental MDA level in PE women had significant negative correlation with serum Se level (r = -0.353, P < 0.05). A negative correlation was found between erythrocyte catalase activity with birth weight (r = -0.528, P < 0.001). Also, there were a significant negative correlation between serum levels of Cu and Se in the preeclamptic women (r = -0.407, P < 0.05).. Our data demonstrate that elevation of lipid peroxides together with impaired antioxidant defense mechanisms and status of trace metals and the presence of possible interrelationship and crosstalk between those parameters may be related at least partly to the pathogenesis of preeclampsia. Additionally, lipid peroxides and blood oxidative imbalance could be part of the cytotoxic mechanisms leading to endothelial cell injury.

Topics: Adult; Antioxidants; Cross-Sectional Studies; Female; Free Radical Scavengers; Humans; Leptin; Lipid Peroxidation; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Prospective Studies; Trace Elements

Topics: Biomarkers; Biomarkers, Tumor; Chorionic Gonadotropin; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Inflammation; Interleukin-10; Killer Cells, Natural; Leptin; Luteinizing Hormone; Neoplasms; Pre-Eclampsia; Pregnancy; Pregnancy Proteins

The objective of this study was to evaluate the change in maternal serum leptin levels in preeclampsia and to study the relationship between maternal serum leptin and thyroid-stimulating hormone (TSH), body mass index (BMI), newborn weight, and proteinuria. Eighty-five pregnant women were included in this prospective study, of whom 50 were preeclamptic and 35 were normotensive. Maternal serum leptin levels were measured by the radioimmunoassay technique and TSH levels were measured by the electrochemiluminescence immunoassay method. The maternal serum leptin levels of preeclamptic and normotensive pregnant women were compared. In each group, the relationship between maternal serum leptin levels and TSH levels, BMI, newborn weight, and proteinuria was evaluated. The maternal serum leptin level was significantly higher in the preeclamptics than in the normotensive pregnant women. In the preeclamptic group, there was a strong positive correlation between maternal serum leptin levels and BMI (r =- 0.80; p < 0.001), a very weak positive correlation between maternal serum leptin levels and proteinuria (r = 0.305; p < 0.05), and a very weak inverse correlation between maternal serum leptin levels and birth weight (r = -0.377; p < 0.01). In the same group, there was no correlation between maternal serum leptin and serum TSH levels (r = 0.22; p > 0.05; Pearson correlation test). Leptin may be involved in the pathology of preeclampsia, and elevated maternal serum leptin levels may be a marker for the early stages of preeclampsia in pregnant women.

Topics: Adult; Body Mass Index; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Prospective Studies; Proteinuria; Thyrotropin

The purpose of this study was to determine the influence of reduced uteroplacental perfusion pressure on plasma leptin and placental leptin receptor expression in rats that develop hypertension in the third trimester of pregnancy.. The ovarian arteries and abdominal aortae of pregnant Sprague-Dawley rats (n=9) were constricted surgically on day 14 of gestation and were matched with sham controls. Systolic blood pressure and weight were measured biweekly. Maternal plasma leptin levels, placental leptin receptor abundance, fetal number, fetal weight, and placental weight were determined.. Reductions in perfusion pressure induced a significant decrease in maternal plasma leptin. Maternal systolic blood pressure and leptin receptor protein abundance was increased in the experimental group. Litter size and fetal and placental weight were significantly decreased in response to reduced perfusion pressure.. Reduced uteroplacental perfusion pressure reduces litter size, fetal and placental weights, and maternal plasma leptin levels and increases placental expression of leptin receptors.

Topics: Animals; Blood Pressure; Female; Fetal Weight; Leptin; Litter Size; Organ Size; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy, Animal; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Leptin; Uterus

The aim of this study was to estimate the levels of leptin in the amnion, chorion laeve, and placenta and to examine for any differences in leptin levels in these tissues from preeclamptic and normotensive pregnant women.. Fresh samples of amnion, chorion laeve, and placenta were obtained from 10 normotensive and 10 preeclamptic women following vaginal delivery. After repeated washing with Krebs Heinsleit solution, 2 g of each tissue were homogenized separately. Following centrifugation, the supernatant was removed and stored at -80 degrees C for analysis of leptin at a later date. Leptin in supernatants from homogenates was measured using commercially available radioimmunoassay (RIA) Kits. Statistical analysis was performed using student's t-test for independent samples and all results are expressed as mean +/- SEM.. Leptin concentrations were significantly higher in all the three tissues from preeclamptic women when compared to the corresponding tissues from normotensive controls (0.52 +/- 0.1 vs. 1.15 +/- 0.41; 0.99 +/- 0.16 vs. 2.19 +/- 0.71; and 10.28 +/- 1.06 vs. 13.95 +/- 1.13 in the amnion, chorion laeve, and placenta, respectively, from normotensive pregnant women and women with preeclampsia; p < 0.05).. Leptin concentration is significantly raised in fetoplacental tissues from women with preeclampsia. Its role in preeclampsia remains unclear and it is not possible to say from this study if the raised levels of leptin evident in placentas from preeclamptic women are a cause or consequence of preeclampsia, although the latter seems more likely.

Topics: Adult; Amniotic Fluid; Chorion; Female; Humans; Leptin; Placenta; Pre-Eclampsia; Pregnancy

This study aimed to investigate (i) the plasma ghrelin concentration at birth, (ii) the relationship of ghrelin with metabolic hormones, including leptin and insulin, and (iii) its association with anthropometric parameters, in appropriately grown preterm (23-36 weeks gestation) and term (37-42 weeks gestation) newborns.. Blood samples for hormonal assay were obtained from preterm (n = 81) and term newborns (n = 40) within the first 2 h of life and before milk feeding or energy intake. The relationship between plasma ghrelin and other metabolic hormones or anthropometric parameters was evaluated.. Plasma ghrelin was detectable in all studied infants and the concentrations did not differ significantly between term and preterm infants [median (interquartile range): 1.21 (0.86-1.48) nmol/l vs. 1.04 (0.71-1.51) nmol/l, P = 0.52, respectively]. There was no overall significant correlation between plasma ghrelin and gestational age, anthropometric parameters and leptin or insulin. However, when term and preterm infants were analysed independently, plasma ghrelin was inversely correlated with birth weight (r = -0.31, P = 0.05) and body length (r = -0.33, P = 0.04) in the term infant group.. Our findings suggested that plasma ghrelin concentrations were relatively constant at birth, between 23 and 42 weeks gestation, and ghrelin secretion did not appear to undergo gestational age-related variations. An inverse relationship between plasma ghrelin and anthropometric indices in term infants raised the possibility that ghrelin might adopt its physiological role in regulating growth and metabolism at a late stage of gestation (> or = 37 weeks gestation). This phenomenon could be beneficial to term newborns by stimulating their appetite and maintaining an adequate blood sugar level at the most critical period when nutrients from mothers are abruptly terminated after birth.

Topics: Birth Weight; Blood Glucose; Body Size; Cesarean Section; Female; Gestational Age; Ghrelin; Humans; Infant, Newborn; Infant, Premature; Insulin; Leptin; Male; Peptide Hormones; Pre-Eclampsia; Pregnancy

The purpose of this study was to compare adipokines' levels between women with and without preeclampsia based on maternal body mass index (BMI).. This was a cross-sectional study among third-trimester pregnancies with preeclampsia (PIH) compared with normotensive controls. Serum levels of adiponectin, leptin, and resistin were measured before delivery by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA).. The study included 22 normotensive and 77 PIH women. Leptin levels increased with maternal BMI. In patients with severe preeclampsia, overweight, and obese women had increased leptin levels (33.4 +/- 14.8 vs 23.0 +/- 10.8 ng/mL respectively, P = .02), and decreased adiponectin levels (8.4 +/- 5.3 vs 12.6 +/- 6.0 ng/mL, P = .03) compared with normal weight women. In women with BMI <25 kg/m2, adiponectin levels increased in patients with preeclampsia compared with controls (11.5 +/- 5.6 vs 9.6 +/- 4.6 and 7.0 +/- 3.2 ng/mL, respectively, P = .005). There was no association between resistin levels and preeclampsia or maternal BMI.. Women with severe preeclampsia and BMI > or = 25 kg/m2 have decreased adiponectin and increased leptin levels, while normal weight women with preeclampsia have increased adiponectin levels.

Topics: Adiponectin; Body Mass Index; Cross-Sectional Studies; Female; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Pre-Eclampsia; Pregnancy; Resistin

Topics: Adiponectin; Adult; C-Reactive Protein; Endothelium, Vascular; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Pre-Eclampsia; Pregnancy; Proteins; Weight Gain

To evaluate the relationship of endothelin 1 (ET-1) and leptin concentrations in women and newborns following a pregnancy complicated with intrauterine growth restriction (IUGR).. Twenty-five women with a pregnancy complicated with IUGR at 19 different gestational ages were matched with women with uncomplicated pregnancies. Blood samples from the umbilical artery and maternal peripheral venous circulation were collected at delivery, and ET-1 and leptin levels were determined from the blood samples. Data relating to obstetric complications (e.g., pregnancy-induced hypertension), delivery (e.g. mode, birth weight, signs of intrapartum fetal distress, and Apgar scores) were also recorded.. Mean maternal ET-1 (13.4+/-6.2-9.9+/-2.9 pmol/l) and mean fetal ET-1 (14.5+/-4.2-11.7+/-3.1 pmol/l) concentrations were significantly higher when women had experienced pregnancies complicated with IUGR than when they had had normal pregnancies. Mean fetal leptin concentration was significantly lower in the study group (6.8+/-2.2 ng/ml) than in the control group (10.6+/-3.6 ng/ml (P<0.05). However, fetal leptin per kilogram of fetal weight was not significantly different in the study group (3.16+/-1.18 ng/ml) than in the control group (3.23+/-0.96 ng/ml) (P>0.05, paired t-test). However, a statistically significant correlation was observed between fetal leptin concentrations per kilogram of fetal weight and fetal endothelin concentrations in pregnancies complicated with IUGR (r=0.546; P<0.05).. These results suggest the intertwined roles of ET-1 and leptin in the pathophysiology of IUGR. Further studies concerning interaction between these peptides in different pregnancy conditions may provide important information about the actions of ET-1 and leptin on fetal growth.

Topics: Adult; Birth Weight; Body Mass Index; Case-Control Studies; Endothelin-1; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Leptin; Pre-Eclampsia; Pregnancy; Regression Analysis

To clarify the role of leptin and androgens in the pathogenesis of preeclampsia, we wanted to assess role of maternal leptin in women with severe and mild preeclampsia and the effects of sex steroid hormones on leptin production.. The groups consisted of 40 healthy pregnant women (HPW) as well as 55 pregnant women with severe preeclampsia (SPE) and 41 pregnant women with mild preeclampsia (MPE). No significant differences were observed between the three groups regarding age, gestational age and body mass index (BMI). Plasma leptin, total testosterone (T), estradiol (E(2)), dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A) levels were measured. Statistical analysis was achieved with one-way analysis of variance (anova) followed by post hoc multiple comparisons with the Tukey honestly significant difference (HSD) test by using SPSS for Windows statistical computer program, and the Pearson's coefficient of correlation was calculated.. The plasma level of leptin was significantly increased in the SPE and MPE groups (p < 0.001), whereas the plasma level of T was significantly increased only in the SPE group (p < 0.001). However, there was no significant difference in plasma levels of DHEAS among the three groups (p < 0.05). The plasma level of A was significantly decreased in the MPE group (p < 0.05). There was no significant difference in the plasma level of E(2) in the MPE and SPE groups (p < 0.05). There was a significant positive correlation between the plasma levels of leptin and E(2) in the MPE group (r = 0.41, p < 0.001).. We concluded that the elevated plasma levels of leptin and testosterone could contribute to the endothelial dysfunction involved in the pathogenesis of preeclampsia, and that estradiol might lead to an increase in the plasma levels of leptin.

Topics: Adult; Androgens; Androstenedione; Body Mass Index; Case-Control Studies; Dehydroepiandrosterone Sulfate; Estradiol; Female; Gestational Age; Humans; Leptin; Pre-Eclampsia; Pregnancy; Severity of Illness Index; Testosterone

To determine whether cerebrospinal fluid (CSF) and circulating levels of leptin differ between women with preeclampsia and women who had an uncomplicated pregnancy.. Maternal serum and CSF leptin concentrations obtained in the third trimester of the gestation were compared in 16 women with mild preeclampsia and 23 normotensive pregnant women who underwent cesarean section. Before administering local anesthetic for spinal anesthesia, 2 mL CSF and 4 mL venous blood sample were taken and were stored at -30 degrees C until serum and CSF leptin levels were measured by enzyme-linked immunosorbent assay (ELISA).. Mean CSF leptin concentrations were not significantly different between the two groups (preeclampsia 9.7 +/- 4.2 ng/mL, normotensive 13.6 +/- 4.3 ng/mL, p = 0.952). Similarly, mean serum leptin concentrations were similar between the two groups (mild preeclampsia 21.7 +/- 7.1 ng/mL, normotensive 18.3 +/- 6.7 ng/mL, p = 0.698). CSF leptin levels are inversely related to the serum leptin concentrations in preeclamptic patients (r = -0.87, p = 0.000). An inverse relationship was also detected between CSF and serum leptin levels in normotensive pregnant subjects (r = -0.66, p = 0.000).. CSF and serum leptin levels were similar in patients with preeclampsia and normotensive pregnant women. However, the CSF leptin was negatively correlated with the serum leptin concentrations in preeclamptic and normotensive control subjects, suggesting that leptin enters the brain by a saturable transport system. Further work is needed to confirm our findings.

Topics: Adult; Case-Control Studies; Cerebrospinal Fluid; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

We measured maternal plasma leptin concentrations in 55 women with pre-eclampsia and 487 normotensive women to determine whether elevated leptin concentrations were associated with the occurrence of pre-eclampsia.. Maternal blood samples were collected at 13 weeks' gestation, on average. Plasma leptin concentrations were determined using immunoassay. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI).. Leptin concentrations were 78% higher in cases than control subjects (median 34.6 vs. 19.5 ng/ml; p < 0.001). Relative to women with leptin concentrations of < 27.4 ng/ml, those with elevated leptin concentrations (> or = 27.4 ng/ml) experienced a 2.3-fold increased risk of pre-eclampsia (OR 2.3; 95% CI 1.1-4.6). We observed evidence of a strong linear component of trend in risk of pre-eclampsia with increasing maternal plasma leptin concentration. Each 10-ng/ml increase in leptin concentration was associated with a 30% increase in pre-eclampsia risk (OR 1.3; 95% CI 1.1-1.5). Overweight women with elevated leptin concentrations experienced the highest risk of pre-eclampsia (OR 6.4; 95% CI 3.1-13.2) as compared with lean women with no leptin elevations.. Elevated plasma leptin concentration and maternal overweight status appear to be independently associated with an increased risk of pre-eclampsia.

Topics: Female; Humans; Leptin; Maternal Age; Obesity; Pre-Eclampsia; Pregnancy; Prospective Studies; Risk Factors

The placenta is a major source of leptin in the fetomaternal circulation, although its physiological role remains to be clarified. Leptin in the fetomaternal circulation is proposed to be a marker of acute stress in the fetus, and the fetus suffering from pre-eclampsia would be under chronic stress. In 16 pre-eclamptic placentas, the expressions of leptin, hypoxia-inducible factor 1alpha (HIF1alpha) and leptin receptor mRNAs were analyzed by semi-quantitative reverse-transcriptase-polymerase chain reaction and compared with clinical data. The co-expressions of leptin and the isoforms of the leptin receptor were observed in all the pre-eclamptic placentas. Leptin mRNA was significantly augmented in the pre-eclamptic placentas, although the level in fetal plasma was not high. The level of the expression of leptin mRNA was correlated with the placental HIF1alpha mRNA level and fetal body weight, but not with the levels of the leptin receptor isoforms in the pre-eclamptic placentas. This observation may suggest that autocrine/paracrine regulation of leptin exists in the human placenta and is upregulated in the pre-eclamptic placenta.

Topics: Adult; Birth Weight; Cesarean Section; Female; Fetal Blood; Gestational Age; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Protein Isoforms; Receptors, Cell Surface; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription Factors

This study investigated the expression profile of placental leptin and leptin receptor isoforms in preeclampsia, using placental tissue from normal pregnancies that were matched in gestational age and birth weight as controls. A total of 29 cases of preeclampsia were studied by immunohistochemistry, including 16 severe and 13 mild preeclampsia cases. Reverse transcriptase-polymerase chain reaction (RT-PCR) was further performed using RNA extracted from frozen tissue (10 severe preeclampsia, 10 mild preeclampsia, and 20 normal third trimester placentas). In all tissue sections, immunostaining signal was shown in the cytoplasmic compartment of the trophoblastic cells. Both the severe and mild preeclampsia groups showed significantly higher immunostaining for leptin compared with normal controls (p < 0.05), but there was no significant difference between the severe and mild preeclampsia groups (p > 0.05). There was no significant difference in immunostaining for leptin receptor between both severe and mild preeclampsia compared with controls (p > 0.05). RT-PCR showed significantly higher levels of mRNA transcripts of leptin in severe preeclampsia (p < 0.05), but not mild preeclampsia (p > 0.05), compared with normal controls. No significant difference in expression of all the receptor isoforms was demonstrated between both severe and mild preeclampsia groups compared with controls (p > 0.05). In conclusion, we confirmed an up-regulated expression of leptin in placental tissue in preeclampsia. However, there was no difference in the expression of all leptin receptor isoforms in placental tissue between preeclamptic and normal pregnancies. The leptin signal probably does not play a major primary role in the pathogenesis of preeclampsia.

Topics: DNA Primers; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Protein Isoforms; Receptors, Cell Surface; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction

The present study was carried out to compare serum levels of leptin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), homeostasis model assessment--(pancreatic beta-cell function) (HOMA-(%B)) and homeostasis model assessment--(tissue insulin sensitivity) (HOMA-(%S)) in women with mild and severe pre-eclampsia and normotensive pregnant women; and to evaluate the possible relationships between these parameters in the pathogenesis of pre-eclampsia. Seventy-three women were divided into three groups: group A consisted of 20 normotensive pregnant women (NPW); group B consisted of 25 women with mild pre-eclampsia (MPE); and group C consisted of 28 women with severe pre-eclampsia (SPE). Serum level of leptin was measured by enzyme immunoassay using a commercial kit. Serum levels of IGF-I and IGFBP-3 were measured with a two-site immunoradiometric assay. Serum level of insulin was measured by the electrochemiluminescence immunoassay method. HOMA used indices of pancreatic beta-cell function and tissue insulin sensitivity. Differences between groups were compared by one-way analyses of variance and the post hoc Tukey-HSD test for multiple comparisons; however, when a variable was not normally distributed, the Mann-Whitney U test was used. Associations between variables were tested using Pearson's coefficient of correlation. Birth weight was significantly lower (p < 0.001) in the MPE and SPE groups than in the NPW group. Serum levels of leptin and insulin in women with SPE and MPE were significantly higher (p < 0.001) than in NPW. Serum levels of IGF-I and IGFBP-3 were significantly lower in women with SPE and MPE compared with NPW (p < 0.001). The mean HOMA-(%B) level in women with SPE and MPE was significantly higher than in NPW (p < 0.001), whereas the mean HOMA-(%S) level in women with SPE and MPE was significantly lower than in NPW (p < 0.001). In the SPE group, systolic blood pressure correlated significantly with serum levels of IGF-I and leptin (r = 0.375, p < 0.05 and r = 0.495, p < 0.01, respectively). A negative correlation between mean HOMA-(%S) level and serum IGFBP-3 level was noted (r = -0.357, p < 0.05). There was a positive correlation between serum level of IGF-I and mean HOMA-(%B) level in mildly pre-eclamptic women (r = 0.541, p < 0.01). We conclude that pre-eclampsia is associated with insulin resistance; and that existing hyperinsulinemia and insulin resistance in women with pre-eclampsia seem not t

Topics: Adult; Blood Glucose; Case-Control Studies; Female; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Pancreas; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Prospective Studies

Both insulin resistance and inflammation may contribute to the onset of preeclampsia. They also could be interrelated. We studied the relationship between inflammatory cytokines and markers of insulin resistance. During their third trimester, 22 proteinuric preeclamptic women and 16 normotensive controls underwent intravenous glucose tolerance test (minimal model). Preeclamptic women were more insulin-resistant (P = .009), and they had higher levels of serum soluble tumor necrosis alpha receptor II (TNFalpha RII) (P = .002), triglycerides (P = .006), uric acid (P = .001), and leptin (P = .002) than did the controls. However, the study groups did not differ in serum TNFalpha, C-reactive protein (CRP), interleukin-6 (IL-6), sex hormone-binding globulin (SHBG), and high-density lipoprotein-2 (HDL(2))-cholesterol. In multiple regression analysis only SHBG (P = .01) and triglycerides (P = .0036) were associated with insulin sensitivity independently of body mass index (BMI), weight gain, HDL(2)-cholesterol, CRP, TNFalpha, and TNFalpha RII, IL-6, and leptin. We conclude that insulin resistance and the inflammatory markers studied were not associated in established preeclampsia.

Topics: Biomarkers; Case-Control Studies; Female; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Leptin; Pre-Eclampsia; Pregnancy; Receptors, Tumor Necrosis Factor; Regression Analysis; Risk Factors; Sex Hormone-Binding Globulin; Triglycerides; Uric Acid

Altered Doppler flow velocimetry of the uterine arteries during the second trimester is correlated with the risk of developing pre-eclampsia. Serum levels of leptin, a protein regulating body weight and secreted by the placenta, are higher in women with severe pre-eclampsia. We investigated whether alterations of uterine arteries' Doppler flow velocimetry during the early second-trimester scan were accompanied by changes in leptin levels, and whether these changes might be an early risk factor for pre-eclampsia. We retrospectively selected 50 women with altered uterine artery velocimetry at the second-trimester scan who subsequently developed pre-eclampsia (group A) and 100 women who did not develop pre-eclampsia, divided into two groups: 50 women with normal velocimetry at the second-trimester scan (group B) and 50 women with altered velocimetry at the second-trimester scan (group C). Serum leptin levels during the second and third trimesters and bilateral uterine artery resistance index during the second trimester were evaluated. No differences were observed in serum leptin levels in the second trimester among the three groups. During the third trimester, women in group A showed significantly higher serum leptin levels in comparison with women in groups B and C (p < 0.01). Serum leptin levels do not seem to be a useful early marker for the development of pre-eclampsia in the presence of altered uterine blood flow, and may be a late compensatory mechanism or reflect a generalized response of the trophoblast to hypoxic stimuli.

Topics: Adult; Arteries; Biomarkers; Birth Weight; Blood Flow Velocity; Body Mass Index; Female; Fetal Growth Retardation; Gestational Age; Humans; Laser-Doppler Flowmetry; Leptin; Parity; Pre-Eclampsia; Pregnancy; Retrospective Studies; Uterus; Vascular Resistance

The aim of this study was to investigate the changes in serum levels of leptin, cytokines and lipoproteins in women with pre-eclampsia and to evaluate their clinical significance in the pathogenesis of pre-eclampsia. We performed a prospective study involving 45 women with pre-eclampsia in the third trimester of pregnancy and 30 normotensive women in the third trimester of pregnancy. Serum level of leptin was measured by enzyme immunoassay using a Cayman chemical kit. Serum levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, soluble IL-2 receptor (slL-2R), IL-6 and IL-8 were measured by using a non-radioimmunoassay chemiluminescent method. Serum lipid concentrations were measured by an Abbott Aeroset (USA) autoanalyzer. Serum levels of apolipoprotein (Apo)A-I and ApoB were evaluated by nephelometrics assays. Differences between groups were evaluated with Student's unpaired t test and, when a variable was not normally distributed, the Mann-Whitney U test was used. The relationship between the variable was explored by the Pearson correlation test. Serum levels of leptin, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 in the pre-eclamptic women were significantly higher than in normotensive women (p < 0.001). In the pre-eclamptic women serum levels of triglycerides, total cholesterol and low-density lipoprotein (LDL)-cholesterol were significantly increased (p < 0.001), while high-density lipoprotein (HDL)-cholesterol and Apo-A were significantly decreased compared to levels in normotensive pregnant women (p < 0.001). No significant differences were noted between the groups in Apo-B (p > 0.05). Serum levels of TNF-alpha were significantly correlated with the serum levels of IL-6, IL-8, triglycerides, sIL-2R, Apo-A and hematocrit in pre-eclamptic women (r = 0.418, p < 0.05; r= 0.389, p < 0.01; r=0.312, p < 0.05; r= -0.318, p < 0.05; r= -0.340, p < 0.05 and r=0.41, p < 0.01, respectively). A negative correlation was seen between serum level of leptin and both IL-1beta and Apo-A in pre-eclamptic women (r=-0.44, p < 0.05; r=-0.39, p < 0.05, respectively). Serum levels of IL-6 were also significantly correlated with the serum levels of HDL-cholesterol, LDL-cholesterol and body mass index (BMI) in pre-eclamptic women (r=0.40, p < 0.01; r=-0.568, p < 0.01; r= -0.30, p < 0.05, respectively). In addition, serum level of IL-8 were significantly correlated with the serum levels of HDL-cholesterol, total cholesterol and BMI in pre-eclamptic women (r= 0.368,

Topics: Apolipoprotein A-I; Apolipoproteins B; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cytokines; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Leptin; Lipoproteins; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; Receptors, Interleukin-2; Receptors, Leptin; Triglycerides; Tumor Necrosis Factor-alpha

The mechanism for the increased microvascular permeability which, underline many of the complications of pre-eclampsia, remain unexplained. It has been suggested that a factor present in the maternal circulation in pregnancies complicated by the disease may be responsible for increased microvascular permeability. In this study, we have investigated the relationship between filtration capacity (K(f)), an index of microvascular permeability, and maternal levels of VEGF, leptin and TNF-alpha, all of which are known permeability factors whose plasma levels are increased in pre-eclampsia.. We used a small cumulative pressure step venous congestion plethysmography protocol to compare K(f), an index of microvascular permeability, during the third trimester of 20 women with pre-eclampsia, 18 normal pregnant women and 18 non-pregnant female matched controls. Blood samples were obtained to measure plasma levels of VEGF, leptin, TNF-alpha plasma protein concentrations and full blood count.. Microvascular filtration capacity (K(f)) was significantly increased in pre-eclampsia compared to the other groups (P<<0.0001, ANOVA). K(f) was also increased in the normal pregnant group when compared to the non-pregnant controls (P=0.02). Plasma levels of VEGF, leptin and TNF-alpha were significantly greater in pre-eclampsia compared to normal pregnancy and non-pregnant controls (P<0.0001, ANOVA, for all three analyses). Total plasma protein and albumin concentrations were significantly lower in the normal pregnant and pre-eclamptic groups, compared to the non-pregnant controls (P<0.0001, ANOVA). K(f) was significantly related to TNF-alpha in pre-eclampsia (r=0.53, P=0.018), and with VEGF in the non-pregnant controls (r=0.6, P=0.02). No significant relationship was observed between K(f) and VEGF, leptin and TNF-alpha during normal pregnancy. There was a significant inverse correlation between plasma albumin concentration and filtration capacity in the normal pregnant (r=-0.94, P<0.0001) and non-pregnant (r=-0.87, P<0.0001) groups but not in the women with pre-eclampsia (r=-0.18, P=0.8).. These data show that that microvascular filtration capacity is significantly increased in pre-eclampsia, and correlates with circulating levels of TNF-alpha but not leptin or VEGF.

Topics: Adult; Analysis of Variance; Capillary Permeability; Endothelial Growth Factors; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Lymphokines; Plethysmography; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Tumor Necrosis Factor-alpha; Uric Acid; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

To study the correlation between amniotic fluid leptin levels and maternal serum leptin levels during the early second trimester, and to determine whether the ratios of amniotic fluid leptin levels to maternal serum leptin levels are elevated in pregnant women who subsequently develop preeclampsia.. Samples from 120 pregnant women were included in this prospective study, of which 20 were from pregnant women who subsequently developed preeclampsia and 100 were from normal pregnant women. Both the amniotic fluid and the maternal serum leptin levels were ascertained by radioimmunoassay (RIA).. A strong correlation between amniotic fluid leptin levels and maternal serum leptin levels was observed in both preeclamptic and normal pregnant women. In addition, the ratios of amniotic fluid leptin levels to maternal serum leptin levels were positively correlated to amniotic fluid leptin levels, but negatively correlated to maternal serum leptin levels. Furthermore, the ratios of amniotic fluid leptin levels to maternal serum leptin levels in preeclamptic women were significantly higher than those in normal pregnant women.. Amniotic fluid leptin levels correlated with maternal serum leptin levels during the early second trimester. The ratios of amniotic fluid leptin levels to maternal serum leptin levels were elevated in preeclamptic women. However, the maternal serum leptin levels themselves showed no such elevation. Therefore, this elevated ratio may be a marker at the early stage of pregnancy in preeclamptic women.

Topics: Adult; Amniocentesis; Amniotic Fluid; Body Mass Index; Female; Gestational Age; Humans; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Regression Analysis

Epidemiological studies demonstrate a relation between preeclampsia (PE) and an increased risk of maternal coronary heart disease (CHD) in later life. However, there are few data available to explain any underlying mechanism. We recruited 40 primigravid women with a history of proteinuric PE delivering between 1975 and 1985 and 40 controls, matched as a group for time of index pregnancy, smoking, and current body mass index to assess classic (lipids, blood pressure) and novel (adhesion molecules, insulin, leptin) risk factor pathways. Women with a history of PE had higher diastolic blood pressure compared with controls (83 vs 76 mm Hg, P<0.05), but there were no significant differences in fasting lipoprotein concentrations (P>0.20). However, concentrations of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 (ICAM-1) in particular were higher in the PE group by 14% (P=0.038) and 44% (P=0.002), respectively. The cases also demonstrated a tendency toward higher fasting insulin (P=0.08) concentrations and had higher glycosylated hemoglobin levels (P=0.004). Leptin concentrations were not significantly elevated. Interestingly, significantly more of the women with history of PE were classified as menopausal (37.55% vs 17.5%, P=0.045). The differences in ICAM-1 concentration persisted (P=0.010) after adjustment for potential confounders, including hormonal use/menopausal status, antihypertensive or lipid-lowering therapy, and social class. We conclude that classic risk factors alone cannot fully explain the elevated CHD risk in women with a history of PE. Rather markedly elevated ICAM-1 concentrations and specific but subtle features of the metabolic syndrome (glucose, blood pressure) are likely to be involved.

Topics: Adult; Biomarkers; Blood Pressure; Cell Adhesion Molecules; Coronary Disease; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin; Leptin; Lipoproteins; Middle Aged; Pre-Eclampsia; Pregnancy; Risk Factors

To investigate placental leptin production in placental insufficiency, placental leptin production was measured in women with severe preeclampsia (group 1) and in normotensive pregnancies associated with intrauterine growth restriction (group 2), compared to controls (group 3). Placental leptin content was increased 3-fold in group 1 compared to group 2 (192.5.1 +/- 39.5 vs. 67.8 +/- 10.6 ng/g) and 8-fold in group 1 compared to group 3 (192.5.1 +/- 39.5 vs. 25.4 +/- 6.9 ng/g). Placental leptin content was positively correlated with maternal leptin/BMI ratio (r = 0.62) and the resistance index of the umbilical artery (r = 0.60). These data demonstrate that placental insufficiency is associated with a dramatic increase in placental leptin production. This results in a rise in maternal leptinemia that may be taken as an early index of placental dysfunction.

Topics: Adult; Birth Weight; Body Mass Index; Cross-Sectional Studies; Female; Fetal Blood; Fetal Growth Retardation; Humans; Leptin; Organ Size; Placenta; Placental Insufficiency; Pre-Eclampsia; Pregnancy; RNA, Messenger; Umbilical Arteries; Vascular Resistance

The purpose of this study was to determine whether maternal serum inhibin A and leptin concentrations changed in the first trimester of pregnancy in patients in whom severe preeclampsia subsequently developed.. Blood samples were collected prospectively from patients during the first trimester of prenatal care. Patients in whom severe preeclampsia with no evidence of glucose intolerance or gestational diabetes mellitus subsequently developed were identified (study group, 30 patients) and matched with control subjects in a 1:2 ratio (control group, 60 patients). Inhibin A and leptin concentrations were determined in these first-trimester serum samples for both the study and control groups.. Leptin levels were correlated highly with body mass index in both groups but were not correlated with the subsequent onset of preeclampsia. Serum inhibin A concentrations were significantly higher in women in whom preeclampsia subsequently developed than in women in whom it did not. With a specific cutoff value, the estimated odds for severe preeclampsia were almost five times higher in women with high inhibin A concentrations than in women with normal levels (odds ratio, 4.93; 95% CI, 1.83, 13.28).. High serum inhibin A levels in the first trimester of pregnancy could be used as an early risk marker for preeclampsia.

Topics: Adult; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inhibins; Leptin; Maternal Age; Odds Ratio; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Pregnancy, High-Risk; Probability; Prospective Studies; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

This study was designed to examine the leptin levels of preeclamptic women and their offspring, to compare them with those of normal pregnant women and to search for a correlation between maternal and fetal plasma leptin levels and their anthropometric characteristics. Twenty-one preeclamptic women and their babies were enrolled into the study. Control group consisted of 21 normal pregnant women and their babies, whose birth weights, gestational ages, and genders match with those of babies born to preeclamptic women. Median maternal leptin concentrations of the preeclamptic group (15.3 ng/mL) were significantly higher ( p = 0.03) than the control group (10.4 ng/mL). However, fetal plasma leptin concentrations were not different ( p = 0.06) between the two groups. Fetal plasma leptin levels were correlated with birth weight, length, body mass index, gestational age, and fetal hematocrit levels in the control group. However, no correlation between leptin levels and these parameters was found in the preeclamptic group. Therefore, preeclampsia may be thought to disrupt normal leptin physiology.

Topics: Adult; Case-Control Studies; Female; Fetal Blood; Humans; Infant, Newborn; Leptin; Linear Models; Male; Pre-Eclampsia; Pregnancy; Reference Values

To measure serum concentrations of the hormone leptin during late pregnancy in Black African women with pre-eclampsia, healthy normotensive pregnant women as controls and healthy normotensive non-pregnant women; secondly, to explore the relationship between leptin and obesity.. Observational, cross sectional study.. Antenatal clinics, antenatal wards, gynaecology out patient and family planning clinics of a tertiary hospital, Durban, South Africa.. Pregnant and non-pregnant Black African women.. Serum leptin was measured by a homologous radio-immunoassay technique. Simple anthropometric parameters were used to explore the relationship between leptin and obesity. In each group, leptin levels were compared between obese (body mass index, BMI > or = 30 kg m(-2)) and lean women.. Serum leptin concentrations, anthropometric parameters, mean blood pressures and proteinuria.. There were 68 women with pre-eclampsia, 92 healthy normotensive pregnant women (controls) and 32 healthy normotensive non-pregnant women. Serum leptin levels were higher in pregnant compared with non-pregnant women [26.66 (1.96) and 25.89 (1.65) vs 17.97 (2.11) ng/mL, P = 0.02]. Weight and BMI showed the greatest correlation with leptin both in pregnant (r = 0.61 and r = 0.58, respectively) and non-pregnant women (r = 0.74 and 0.79, respectively). There was no significant difference in the mean concentrations of leptin between women with and those without pre-eclampsia [26.66 (1.96) vs 25.89 (1.65) ng/mL, respectively, P = 0.95].. Pregnancy is a hyperleptinaemic state. There is no difference in serum leptin levels between Black African women with pre-eclampsia and healthy normotensive pregnant women. Serum leptin concentration is largely determined by the degree of adiposity.

Topics: Adult; Blood Pressure; Body Mass Index; Cross-Sectional Studies; Female; Humans; Leptin; Obesity; Parity; Pre-Eclampsia; Pregnancy; South Africa

The objective of this study was to compare umbilical cord plasma leptin between infants of mothers who experienced preeclampsia and infants of control subjects and to study the relation between cord plasma leptin and infant obesity, as indicated by ponderal index.. On the basis of a population of approximately 13,000 deliveries, we compared cord plasma leptin from preeclamptic (n = 256 women) and control pregnancies (n = 607 women) after taking the differences in gestational age and ponderal index into account.. Cord plasma leptin increased strongly with gestational age, both in the preeclampsia group and the control subjects (P <.01), but at each gestational age the preeclampsia group had higher leptin levels than control subjects (P <.01). Adjustment for the higher ponderal index among control subjects (P <.05) did not alter the difference in leptin levels between the groups.. We found higher levels of umbilical cord plasma leptin in infants of mothers who had preeclampsia (compared with infants of control subjects) after adjusting for differences in gestational age, gender, and infant ponderal index.

Topics: Adult; Birth Weight; Female; Fetal Blood; Gestational Age; Humans; Leptin; Pre-Eclampsia; Pregnancy; Reference Values

In many pre-eclamptic women the placentation process seems to be disturbed. Our objective was to investigate if disturbed placentation in pre-eclamptic women may be recognized in early second trimester as altered plasma levels of factors involved in the formation of the uteroplacental unit.. In a prospective study of 2190 pregnant women we compared plasma leptin, transforming growth factor-beta(1) (TGF-beta(1)) and plasminogen activator inhibitor type 2 (PAI-2) concentrations at 18 weeks' gestation in 71 women with subsequent pre-eclampsia and 71 controls matched for age, parity and first trimester body mass index.. Leptin and TGF-beta(1) concentrations were lower and PAI-2 concentration higher in women destined to develop pre-eclampsia relative to controls (leptin: median (25-75 percentiles): 19.0 (14.5-29.0) vs 25.0 (16.0-35.0) ng/ml (p =0.03), TGF-beta(1): 3.2 (2.0-6.1) vs 5.3 (3.8-7.1) ng/ml (P=0.01) and PAI-2: 78.8 (65.1-118.1) vs 67.6 (61.6-79.6) ng/ml (P=0.002)). OR (95 per cent CI) for pre-eclampsia for women in the upper quartile compared to women in the lower quartile were: leptin: 0.2 (0.03-0.7), TGF-beta(1): 0.2 (0.08-0.7) and PAI-2: 3.1 (1.2-8.2).. Altered plasma concentrations levels of factors involved in the process of placentation in women destined to develop pre-eclampsia, indicate that disturbed formation of the uteroplacental unit is reflected in the maternal circulation before 20 weeks' gestation.

Topics: Adult; Biomarkers; Female; Humans; Leptin; Odds Ratio; Placentation; Plasminogen Activator Inhibitor 2; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Prospective Studies; Transforming Growth Factor beta; Transforming Growth Factor beta1

Susceptibility genes present in both mother and fetus most likely contribute to the risk of pre-eclampsia. Placental biopsies were therefore investigated by high-density DNA microarray analysis to determine genes differentially regulated within chorionic villous tissue in pre-eclampsia and normal pregnancy. The pooled RNAs of pre-eclamptic and normotensive subjects were hybridized to the HuGeneFL array representing sequences from approximately 5600 full-length human cDNAs. The differentially expressed genes that were detected could be categorized into nine groups: adhesion molecules, obesity-related genes, transcription factors/signalling molecules, immunological factors, neuromediators, oncogenic factors, protease inhibitors, hormones and growth factor-binding proteins. Among those, the obesity-related genes included putative candidate genes associated with the pathogenesis of pre-eclampsia. One of the most up-regulated transcripts was the obese gene (43.6-fold change), and this was reflected by elevated leptin protein levels. In the case of feto-maternal contribution of polymorphic genes to pre-eclampsia, expression analysis of placental tissue has lead to numerous target genes waiting for large scale genetic linkage analyses.

Topics: Female; Gene Expression Profiling; Humans; Integrin alpha Chains; Leptin; Obesity; Oligonucleotide Array Sequence Analysis; Placenta; Pre-Eclampsia; Pregnancy; Up-Regulation

To investigate whether hypertensive disorders of pregnancy alter the maternal and fetal leptin levels.. Fifty primigravidas between 28 and 34 weeks of gestation were divided into three groups: group A consisted of 17 normal pregnant women with a mean gestational age of 31 weeks, group B consisted of 15 women with gestational hypertension without proteinuria with a mean gestational age of 30 weeks and group C consisted of 18 pre-eclamptic women with a mean gestational age of 31 weeks.. The pre-eclamptics had significantly higher serum leptin levels than those in normal pregnancies (p<0.001) but no difference was noted between normal and gestational hypertensive pregnancies. Pre-eclamptic women had significantly higher umbilical vein leptin levels (4.68+/-1.66ng/ml) compared to normal pregnancies (1.92+/-0.71ng/ml) and those with gestational hypertension (2.47+/-0.81ng/ml).. Pre-eclampsia is associated with an increase in maternal plasma leptin levels and fetal of leptin production increases in gestational hypertension and even more in pre-eclampsia.

Topics: Adult; Female; Fetal Blood; Humans; Hypertension; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Reference Values

Serum leptin levels increase during pregnancy and this increase is more pronounced in women with preeclampsia.. To determine if there is a significant correlation of serum leptin with insulin and glucose levels in normotensive pregnant women and in preeclampsia patients.. A nested case-control study in 16 normotensive pregnant women and in 16 preeclampsia mestizo Mexicans in the third trimester of the gestation matched by age, gestational age and pre gestational body mass index. Venous blood samples after at least 6 h fast, were obtained and stored at -70 degrees C to measure serum leptin levels by ELISA, insulin concentrations by RIA and glucose by the glucose oxidase technique.. There were no differences between normotensive women and those with preeclampsia in serum leptin, insulin and glucose levels. There was a positive correlation between leptin and insulin concentrations (p = 0.005), a negative correlation between leptin and glucose levels (p = 0.02) and no correlation between leptin and pre gestational body mass index.. In this study, women with preeclampsia did not have higher leptin levels than normotensive pregnant women.

Topics: Adult; Blood Glucose; Case-Control Studies; Female; Humans; Insulin; Leptin; Mexico; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

Plasma leptin levels in preeclamptic patients have been reported to be similar compared to those of normotensive pregnant women. Nonetheless, no reports have dealt with the effect of antihypertensive treatment and leptin in preeclamptic patients.. The study involved three groups of a similar age, body mass index and weeks of gestation. The groups were 30 normal pregnant women and 23 pregnant women with severe preeclampsia (SPE). The SPE patients were not treated prior to admission and the treatment was a single dose of alpha-methyldopa or hydralazine alone or in combination. The samples were taken at random in the afternoon (isotonic saline or pharmacological treatment) and 1 h before and after the treatment was given. Leptin serum levels were determined by a commercial sandwich ELISA assay.. Leptin levels of the SPE group prior to the treatment were similar to the levels recorded for the normal pregnant women. However, after 1 h leptin levels were significantly higher (p < 0.001) in the nontreated patients (8.0 +/- 1.5) compared with those treated (5.15 +/- 0.9).. These marked differences between treated and nontreated patients suggest that leptin levels may be modulated by a single antihypertensive treatment in preeclamptic patients with a discrete increase in blood pressure.

Topics: Adult; Antihypertensive Agents; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Hydralazine; Leptin; Methyldopa; Pre-Eclampsia; Pregnancy

To compare maternal serum leptin concentration in women with pre-eclampsia and women with normal pregnancy, and to evaluate the relationships between leptin and several inflammatory cytokines.. Prospective clinical study.. University Hospital of Puerto Real, Cadiz, Spain.. Twenty-seven women with pre-eclampsia and 25 normotensive pregnant women.. Maternal serum levels of TNF-alpha, TGF-beta1, interleukin 6, and leptin were measured using a commercially available immunoassay.. Maternal serum levels of leptin and its relationship to levels of TNF-alpha, TGF-beta1 and interleukin 6.. Maternal serum leptin levels were higher in women with pre-eclampsia, but this difference was of borderline statistical significance (median 15.9 ng/mL; interquartile range (5.4-31.9) vs 30.5 ng/mL (13.9-64) (P = 0.05). The concentration of maternal serum leptin was correlated with pre-gestational and gestational body mass index (r = 0.45, P = 0.03; r = 0.44, P = 0.04), TNF-alpha concentration (r = 0.57, P = 0.002) and interleukin-6 level (r = 0.46, P = 0.02) in women with normal pregnancy. In women with pre-eclampsia, only a significant correlation between maternal serum leptin level and TNF-alpha concentration (0.47, P = 0.01) was found.. The level of maternal serum leptin is increased and correlates positively with the level of TNF-alpha in women with pre-eclampsia. In women with a normal pregnancy leptin levels not only correlate with TNF-alpha, but also with IL-6 and body mass index.

Topics: Adult; Cytokines; Female; Humans; Immunoassay; Interleukin-6; Leptin; Lymphotoxin-alpha; Pre-Eclampsia; Pregnancy; Prospective Studies; Tumor Necrosis Factor-alpha

To study the effect of maternal pre-eclampsia on cord plasma leptin concentrations in preterm infants.. Leptin concentration was analysed in cord plasma of 74 preterm infants, gestational age 24 to 32 weeks. Of these, 14 were born to pre-eclamptic mothers, in 10 intrauterine growth retardation (IUGR) was present, and 59 had been exposed antenatally to corticosteroids.. The mean (SD) concentration of cord plasma leptin was 1.31 (0.88) microg/l. A significant correlation was found between leptin concentration and gestational age (r = 0.336; p = 0.0037). Leptin levels were higher in infants of pre-eclamptic mothers (p = 0.0007), in those with IUGR (p = 0.0005), and in infants exposed antenatally to corticosteroids (p = 0.02). In multiple regression analysis, leptin was associated with gestational age and maternal pre-eclampsia (both p < 0.05), but not with antenatal corticosteroids.. Increased fetal leptin in maternal pre-eclampsia may reflect a physiological adaptation to fetal stress such as hypoxia.

Topics: Birth Weight; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Leptin; Male; Maternal-Fetal Exchange; Pre-Eclampsia; Pregnancy

The number of patients with hypertension, obesity, diabetes, and hyperlipidemia is increasing. This tendency is observed in pregnant women, in whom many obstetrical and perinatal complications occur. The prevention of these abnormalities is important in reducing perinatal mortality and the risk of coronary disease. We established a pregnant rat model with diabetes and signs and symptoms mimicking preeclampsia. On day 6 of pregnancy, streptozotocin (STZ) or citrate buffer was injected into the tail vein. After STZ administration, plasma glucose was increased within 48 hours and sustained at a high level until day 20 of pregnancy, and plasma insulin was decreased. Fetuses from STZ-treated mothers were growth-restricted, and plasma glucose was 6-fold higher in fetuses of STZ-treated versus control rats. The systolic blood pressure, urinary protein, and hematocrit were increased significantly in STZ-treated rats. Total cholesterol and triglycerides were also elevated in STZ-treated rats, but plasma leptin levels were decreased. The STZ-induced diabetic pregnant rat model exhibited preeclampsia, hemoconcentration, hyperlipidemia, hypoleptinemia, and intrauterine growth restriction. This model closely mimics the features of human pregnancy complicated by diabetes and is useful for the basic study of the pathophysiology of pregnancy with diabetes.

Topics: Animals; Diabetes Mellitus, Experimental; Disease Models, Animal; Female; Hypertension; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Rats; Rats, Wistar; Streptozocin

We measured bound and free leptin levels in preeclamptic and matched normal pregnant and never-pregnant women to determine whether the free component of leptin is increased during pregnancy and further increased in preeclampsia. Two milliliters of serum was obtained from 18 normal and 18 preeclamptic patients matched by pre-pregnancy body mass index (BMI), and from 18 never-pregnant women matched by BMI with the pregnant groups. The sample was subjected to gel filtration using Sephadex G-100. Radioimmunoassay (RIA) was performed on all fractions, and the proportions of bound and free leptin were determined by analyzing the areas under the curve of the chromatographic profile. The total maternal serum leptin concentration was significantly higher in normal pregnancy compared with the nonpregnant state and was further increased in preeclampsia (33.8 +/- 4.1 v 15.2 +/- 1.8 ng/mL, P = .002, and 48.1 +/- 5.6 ng/mL, P = .02, respectively). Free leptin was increased in normal pregnant compared with never-pregnant women (25.9 +/- 4.1 v 11.0 +/- 2.0 ng/mL, respectively, P = .01), while the increase of total leptin in preeclampsia was exclusively in the free fraction that was significantly higher versus the normal pregnant group (41.8 +/- 5.6 v25.9 +/- 4.1 ng/mL, respectively, P = .01). The bound leptin fraction, by contrast, was significantly increased in the normal pregnant group compared with the preeclamptic group and the never-pregnant group (7.9 +/- 0.56 v 6.2 +/- 0.36 and 4.1 +/- 0.36 ng/mL, respectively, P = .009 and P = <.0001). In conclusion, the free leptin concentration increases in normal pregnancy and is further increased in preeclampsia. This supports the hypothesis that biologically active leptin is elevated in normal pregnancy and is increased more in women with preeclampsia.

Topics: Adult; Body Mass Index; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy; Protein Binding; Reference Values

Leptin concentrations have been found to be elevated in cross-sectional studies of established pre-eclampsia. Circulating concentrations of leptin were measured in a cross-sectional study to confirm these findings (19 women with pre-eclampsia and 13 normal pregnant controls) and in a longitudinal study to establish the timing of the increase in leptin concentrations (samples obtained at 16, 20, 24, 28, 32, 36 and 38 weeks gestation from eight women who went on to develop pre-eclampsia and seven normal pregnant controls). In the cross-sectional study, plasma leptin concentrations were significantly greater in women with pre-eclampsia than in normal controls (P: = 0.001). In the longitudinal study, it was found that circulating leptin concentrations rose gradually to 32 weeks and thereafter declined slightly in normals. The concentrations in women destined to develop pre-eclampsia were consistently higher from 20 weeks gestation (P: = 0.04-0.003) and, in contrast to the normal controls, rose markedly from 32 weeks as pre-eclampsia developed. This study confirms that plasma leptin concentrations are increased in established pre-eclampsia and reports for the first time that leptin concentrations are elevated before pre-eclampsia is clinically evident.

Topics: Adult; Blood Pressure; Body Mass Index; Cross-Sectional Studies; Female; Gestational Age; Humans; Leptin; Longitudinal Studies; Platelet Count; Pre-Eclampsia; Pregnancy; Uric Acid

The aim of this study was to evaluate the serum leptin levels in preeclampsia patients and in normotensive pregnant women, as well as, to assess an association with the severity of the disease. A cross-sectional study was carried out in 14 patients with mild preeclampsia, 12 with severe preeclampsia, and in 32 normotensive pregnant women during the third trimester of pregnancy. Rigorous criteria of selection were considered. The leptin levels were tested by an enzyme-linked immunosorbent method. There were no significant differences in serum leptin concentrations between the patients with mild preeclampsia [13.6 +/- 11.2 (95% CI, 7.7-19.4) ng/mL], severe preeclampsia [14.8 +/- 11.5 (95% CI, 8.2-21.3) ng/mL] and normotensive pregnant women [12.5 +/- 7.9 (95% CI, 9.7-15.2) ng/mL]. In conclusion, serum leptin levels were similar in the patients with different grades of preeclampsia and normotensive pregnant women.

Topics: Adult; Blood Pressure; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Leptin; Pre-Eclampsia; Pregnancy

The aim of the study was to investigate cord blood leptin concentrations and their relationship to birth weight and gender in term pregnancies complicated by pre-eclampsia. Cord blood samples were obtained from 52 women, identified as having pre-eclampsia, and their newborns (31 males and 21 females) immediately after birth. Specimens were analyzed using a human leptin 125I radioimmunoassay. The relationship between leptin and anthropometrics was assessed by Spearman correlation. Differences in cord blood leptin levels between male and female infants were tested with the Mann-Whitney U test. The correlation between leptin and gender was computed using the product-moment-biseral correlation analysis for continuous and dichotomous variables. The multiple logistic regression analysis examined influences of sex, birth length, birth weight, birth weight/birth length ratio, ponderal index and maternal leptin as covariates on the fetal cord leptin level. Fetal leptin correlated positively with birth weight, length and weight/length ratio, in the total group and in the male subgroup and additionally with ponderal index in the female subgroup. Cord blood leptin concentrations in female newborns were significantly higher than in male newborns (p = 0.015), and concentrations correlated with gender (r = -0.315; p = 0.023). Multiple logistic regression analysis revealed four potential independent factors influencing fetal cord leptin: gender, birth weight, birth weight/birth length ratio and maternal leptin. In conclusion, cord leptin concentrations in pregnancies complicated by pre-eclampsia correlate positively with birth weight and gender. Leptin concentrations in female newborns are higher compared to male newborns.

Topics: Adult; Antihypertensive Agents; Birth Weight; Female; Fetal Blood; Gestational Age; Humans; Hypertension; Infant, Newborn; Labetalol; Leptin; Magnesium; Male; Multivariate Analysis; Pre-Eclampsia; Pregnancy; Proteinuria; Regression Analysis; Sex Factors

We determined the serum levels of leptin in 96 pregnant women with body mass index between 20 to 30, 30 normal (NP), 26 with mild preeclampsia (MPE), 27 with severe preeclampsia (SPE), 6 with chronic hypertension plus preeclampsia (CHT+PE) and 7 with chronic hypertension (CHT). A significant (p < 0.01) decrease in leptin levels was observed in the SPE group when compared with the NP group. On the contrary, significant (p < 0.05) increases were observed in the CHT and CHT+PE groups when compared with the NP group. Leptin levels were significantly higher in the MPE (p < 0.001), CHT (p < 0.01) and CHT+PE (p < 0.5) groups when compared with the SPE. No significant differences were observed in the CHT group when compared with CHT+PE. Moreover, a positive correlation was encountered (r = 0.6, p < 0.001) between platelet number and leptin levels for all the patients with preeclampsia. These results suggest that leptin levels may be useful metabolic parameter in different types of hypertension during pregnancy.

Topics: Adult; Case-Control Studies; Female; Humans; Hypertension; Leptin; Platelet Count; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

This paper is a summary of results obtained in our studies on leptinemia in patients with chronic renal failure treated with recombinant human erythropoietin (rHuEPO), in kidney transplant patients, in patients with essential hypertension, and in pregnant women with preeclampsia. In this study, we found that rHuEPO treatment has a suppressive effect on leptinemia in patients with endstage renal failure. These results suggest that the appetite stimulating effect of rHuEPO may be mediated by a reduction of leptin synthesis and release. At the early stage of successful kidney transplantation, a significant decline of leptinemia was noticed, which was not related either to the excretory function of the graft or the kind and dose of immunosuppressants. In kidney transplant patients with grafts functioning well for 2.5 years, significantly elevated leptinemia was found. From these results, we may conclude that factors other than the excretory function of the graft and the kind and dosage of immunosuppressants may be involved in the pathogenesis of abnormal leptinemia in these patients. Both in normotensive subjects and patients with essential hypertension, a positive correlation was found between leptinemia and mean blood pressure, suggesting that leptin may be involved in the regulation of blood pressure. Both healthy and preeclamptic pregnant women show higher leptinemia than nonpregnant women. In preeclamptic women, leptin levels in maternal vein blood, umbilical cord blood, and amniotic fluid were significantly higher than respective values found in healthy pregnant women. In contrast to healthy pregnant and nonpregnant women, in women with preeclampsia, no correlation was found between the body mass index (BMI) and leptinemia. In preeclamptic women the abnormally elevated leptinemia was not related to blood pressure. Finally, no correlation was found between leptinemia in maternal and umbilical cord blood. From these studies, it follows that the elucidation of abnormal leptin secretion in the pathogenesis of preeclampsia needs further study.

Topics: Adipose Tissue; Amniotic Fluid; Appetite; Blood Pressure; Blood Proteins; Body Mass Index; Erythropoietin; Female; Fetal Blood; Humans; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Pre-Eclampsia; Pregnancy; Proteins

We tested the hypothesis that the maternal leptin concentration would be increased in preeclampsia, independent of maternal obesity.. Maternal and cord plasma leptin concentrations were compared in 2 groups of women with either preeclampsia (n = 24) or normal pregnancy (n = 24), matched 1:1 for prepregnancy body mass index and fetal gestational age at sampling.. Median leptin concentrations were significantly higher (P <. 03) in women with preeclampsia (45.6 ng/mL) than in normal pregnant women (27.0 ng/mL) and fell rapidly shortly after delivery (26.7 ng/mL and 25.4 ng/mL, respectively). Cord leptin was not significantly different between groups (5.4 ng/mL and 5.8 ng/mL, respectively). Maternal and cord leptin correlated significantly (rho = 0.76, P <.01) only in preeclampsia.. Preeclampsia is associated with an increase in maternal plasma leptin concentrations that strongly correlates with the fetal cord concentration at delivery.

Topics: Adult; Birth Weight; Body Mass Index; Case-Control Studies; Female; Fetal Blood; Gestational Age; Humans; Leptin; Longitudinal Studies; Pre-Eclampsia; Pregnancy; Proteins

The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.

Topics: Adipose Tissue; Adolescent; Adult; Blood Pressure; Body Mass Index; Case-Control Studies; Cohort Studies; Confounding Factors, Epidemiologic; Female; Humans; Leptin; Obesity; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Proteins; Risk Factors; Statistics as Topic; Sweden

The objective of the present study was to examine the impact of preeclampsia on the relation of leptin and neuropeptide Y (NPY) gene expression in human placenta. A second goal was to monitor the change of leptin messenger RNA (mRNA) with increasing gestational age. Placental tissue was obtained from 17 premature deliveries, 18 term deliveries, and 10 mothers with preeclampsia. Gene expression of leptin, NPY, and two housekeeping genes (beta-actin and glyceraldehyde-3-phosphate dehydrogenase was quantified using real-time PCR. The leptin/beta-actin mRNA ratio was significantly higher in specimens of patients with preeclampsia than in those of gestational age-matched controls (0.63+/-0.23 vs. 0.09+/-0.04 relative U (RU); P = 0.03). NPY/beta-actin mRNA was significantly reduced in the preeclampsia group (0.003+/-0.001 vs. 0.026+/-0.008 RU in controls; P = 0.01). The NPY/leptin ratio was 0.11+/-0.09 for preeclamptic placenta samples and 1.7+/-0.6 RU for the controls (P = 0.02). The leptin/beta-actin ratio was significantly lower in placenta from premature deliveries than in term deliveries (0.02+/-0.004 vs. 0.12+/-0.05 RU; P = 0.01). Similar results were obtained for normalization to glyceraldehyde-3-phosphate dehydrogenase mRNA. Our data suggest an increase of placental leptin production with gestational age. In patients with preeclampsia, elevated leptin expression goes along with suppressed NPY expression. This resembles hypothalamic regulation.

Topics: Adult; Female; Gestational Age; Humans; Hypothalamus; Leptin; Neuropeptide Y; Placenta; Pre-Eclampsia; Pregnancy; Proteins; RNA, Messenger

Leptin, an adipose tissue-derived signalling factor encoded by the obese gene has been shown to be present as a 16-kDa protein in the blood of mice and humans. Resistance to leptin occurs in human obesity. Leptin has also been shown to associate with plasma insulin concentrations and there is currently considerable debate about the potential link between insulin resistance and resistance to leptin. In non-pregnant individuals, circulating leptin concentrations associate strongly with both total body fat mass and body mass index (BMI). In normal human pregnancy, the maternal fat stores increase to a peak in the late second trimester, before declining towards term as fat stores are mobilized to support the rapidly growing fetus. Insulin resistance increases during late pregnancy and is believed to be further enhanced in pregnancies complicated by pre-eclampsia. The aim of this study was to examine if leptin levels were altered in pregnancy and, if so, whether the pattern of change in circulating leptin related to previously established changes in fasting insulin concentrations or fat mass.. We measured third trimester plasma leptin concentrations in 12 uncomplicated pregnant women, nine women with pre-eclampsia matched for age and booking BMI, and 18 non-pregnant women similarly matched. We also examined the longitudinal course of leptin concentrations occurring throughout gestation (from 10 weeks gestation and at five week intervals thereafter), in five normal pregnancies and two women with gestational-onset diabetes.. Leptin concentrations were significantly higher in the normal pregnant women (37.1 microg/L, [15.4-117.0], geometric mean, [range]; p=0.049), and women with pre-eclampsia (45.3 microg/L, [21.3-98.4]; p=0.001), than in non-pregnant controls (17.85 microg/L, [1.3-36.5]), however, there was no significant difference between uncomplicated and pre-eclamptic pregnancies (p=0.22). On examination of the longitudinal course of leptin concentrations occurring throughout gestation, in all seven women plasma leptin concentrations initially increased relative to booking (10 weeks) concentrations, but did so by varying amounts (ranging between 30-233%). Significantly, however, in all seven women plasma leptin concentrations peaked at around 20-30 weeks of gestation before declining towards term.. On the basis of these observations, we postulate that plasma leptin levels increase significantly in human pregnancies and that the pattern of change in circulating leptin parallels the process of fat accumulation and mobilization.

Topics: Adult; Biomarkers; Body Mass Index; Cohort Studies; Female; Humans; Leptin; Lipid Mobilization; Longitudinal Studies; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Proteins; Reference Values

Preeclampsia (PE) is a hypertensive disorder, which develops in late pregnancy and is usually associated with placental hypoxia and dysfunction. We have recently demonstrated that leptin is a novel placenta-derived hormone in humans and suggested its significance in human pregnancy (see Ref. 19). To explore the changes in the leptin production in placenta in PE, we measured the plasma leptin level and placental leptin messenger RNA expression in pregnant women with PE. Plasma leptin levels in preeclamptic women were elevated significantly, compared with gestational age- and body mass index-matched normal pregnant women (P < 0.0001). Plasma leptin levels in the severe PE group were significantly higher than those in the mild PE group (P < 0.0001). Plasma leptin levels in preeclamptic women were reduced, soon after the placental delivery, to those expected for their body mass indices. Northern blot analysis revealed that leptin messenger RNA levels are increased in the placentas from preeclamptic women, compared with normal pregnant women. Leptin secretion was increased significantly in a human trophoblastic cell line (BeWo cells) cultured under hypoxic conditions (5% O2), compared with those cultured under standard conditions (20% O2; P < 0.01). The present study demonstrated that placental production of leptin is augmented in severe PE, probably because of placental hypoxia, thereby suggesting the possible significance of leptin as a marker of placental hypoxia in severe PE.

Topics: Adult; Blotting, Northern; Body Mass Index; Cell Hypoxia; Cell Line; Female; Gene Expression; Gestational Age; Humans; Hypoxia; Leptin; Oxygen; Placenta; Pre-Eclampsia; Pregnancy; Protein Biosynthesis; Proteins; RNA, Messenger; Trophoblasts

Leptin is presumed to be related to body mass index (BMI) and body fat stores and is involved together with neuropeptid Y (NPY) in the regulation of appetite. As pregnancy is accompanied both by changes of BMI and appetite, performance of studies presented in this paper were fully justified. In 43 healthy pregnant women and in 18 pregnant women with mild or moderate EPH-gestosis, concentrations of leptin and NPY were estimated in maternal venous blood, umbilical cord blood and in amniotic fluid. The control group consisted of 26 healthy nonpregnant women. Healthy nonpregnant women showed a BMI of 23.08+/-0.65 kg/m2 which was significantly lower than in healthy pregnant women (26.9+/-0.4 kg/m2, p < 0.001) and in women with EPH-gestosis (29.7+/-0.9, p < 0.0001). Also in healthy pregnant women the BMI was significantly lower than in EPH-gestosis subjects (p < 0.001). In healthy nonpregnant women plasma leptin levels were significantly lower than in healthy pregnant and EPH-gestosis women (10.9+/-1.68 vs 14.99+/-1.28 vs 21.89+/-2.58 ng/ml, respectively). In umbilical cord blood plasma leptin levels were significantly lower than in maternal blood only in healthy pregnant women (7.37+/-0.69 vs 14.99+/-1.28 ng/ml) but not in EPH-gestosis subjects (18.06+/-3.38 vs 21.89+/-2.58 ng/ml). Leptin levels in amniotic fluid were significantly lower than in umbilical cord blood both in healthy pregnant women (2.25+/-0.20 vs 7.37+/-0.69 ng/ml) and EPH-gestosis women (6.58+/-2.62 vs 18.06+/-3.38 ng/ml). In EPH-gestosis women leptin levels were significantly higher than in healthy pregnant women in maternal blood (21.89+/-2.58 vs 14.99+/-1.28 ng/ml), umbilical cord blood (18.06+/-3.38 vs 7.37+/-0.69 ng/ml) and amniotic fluid (6.58+/-2.62 vs 2.25+/-0.2 ng/ml). In both examined pregnant groups plasma NPY levels were nonsignificantly lower in healthy pregnant and EPH-gestosis women (42.28+/-4.09 and 43.68+/-8.45 pg/ml, respectively) than in nonpregnant women 50.65+/-6.13 pg/ml). In normal pregnancy a significantly higher NPY level was found in umbilical cord blood as compared with respective values in EPH-gestosis women (116.28+/-17.0 vs 49.65+/-7.01 pg/ml). Finally in both examined groups of pregnant women the amniotic fluid NPY level was of similar magnitude (13.85+/-1.52 and 13.89+/-2.46 pg/ml in healthy pregnant and EPH-gestosis women respectively). No significant correlation was found between fetal birth weight and cord-serum leptin and NPY levels respectively.

Topics: Adult; Amniotic Fluid; Female; Fetal Blood; Humans; Leptin; Maternal-Fetal Exchange; Neuropeptide Y; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Proteins