leptin and Abortion--Habitual

Pregnancy is a proinflammatory and hypercoagulable state. Miscarriage concerns approximately 15% of pregnancies. Recurrent miscarriage is a rather rare condition with an estimated incidence of 1% to 3%. However, despite years of investigation, the etiology is not established in up to 50% of cases. A multidisciplinary approach in the evaluation of miscarriage is essential to understand the cause and risk of recurrence. Although genetic factors are the major cause of spontaneous miscarriages, their relationship with recurrent miscarriage is less frequent. Recently, many kinds of genetic polymorphisms have also been found to be associated. Endocrine disorders such as poorly controlled diabetes, polycystic ovary syndrome, and hypothyroidism are linked with recurrent miscarriage. The relationship between recurrent miscarriage and subclinical thyroid disorders and thyroid autoimmunity is disputed, especially in early miscarriages. Uterine malformations should be considered as a cause of recurrent miscarriage. Although autoimmune-based recurrent miscarriage has been described, mainly antiphospholipid antibodies, the role of alloimmune mechanisms remains poorly understood. The influence of congenital thrombophilia is controversial. Antiphospholipid syndrome or antiphospholipid antibody-related recurrent miscarriage, and some endocrinologic disorders, have a specific and effective treatment. Still, the effectiveness of some common treatments needs to be demonstrated.

Topics: Abortion, Habitual; Cell-Derived Microparticles; Chorionic Gonadotropin; Endocrine System Diseases; Female; Glycodelin; Glycoproteins; Humans; Immune System Diseases; Leptin; Polymorphism, Genetic; Pregnancy; Risk Factors; Uterine Diseases; Uterus

The aim of this study was to investigate whether recurrent pregnancy loss (RPL) is associated with adipokine gene polymorphisms (namely the leptin -2548 (G/A), adiponectin 276 (G/T), and adiponectin 45 (T/G) polymorphisms) and/or adipokine serum levels.. A total of 145 women participated in the study. For the analysis of serum adipokine levels, 19 healthy fertile women (control group) and 60 women suffering from RPL were included. For the polymorphism analysis, 126 women suffering from RPL were included. Serum adipokine levels were determined using a commercial radioimmunoassay kit. Adipokine polymorphisms were analyzed using an allele-specific polymerase chain reaction (PCR).. Our immunoassays revealed that serum leptin levels were similar in control and RPL groups (17.34 and 20.16 ng/mL, respectively). In contrast, serum adiponectin levels were significantly higher in women with RPL than in controls (9.83 and 6.89 μg/mL, respectively; P < 0.05). Unfortunately, our allele-specific PCR experiments did not reveal any significant differences in allele frequency between women with RPL and NCBI allele frequencies.. This study demonstrates that adiponectinemia is increased in patients suffering from RPL. However, association of adiponectin with adverse pregnancy outcomes remains to be elucidated.

Topics: Abortion, Habitual; Adiponectin; Adult; Female; Humans; Leptin

BACKGROUND The aim of this study was to investigate the possible associations of miRNA-27a and Leptin polymorphisms with the risk of recurrent spontaneous abortion (RSA). MATERIAL AND METHODS Between May 2013 and April 2015 at Shenzhen Longhua New District Central Hospital, we randomly recruited 138 RSA patients as the case group and another 142 normal pregnancy women as the control group. We used denaturing high-performance liquid chromatography (DHPLC) to determine the genotypes and allele frequencies of miRNA-27a rs895819 A/G and Leptin rs7799039 G/A. RESULTS The GG genotype and G allele frequencies of miRNA-27a rs895819 A/G were higher in the case group than in the control group, and the AA genotype and A allele frequencies of Leptin rs7799039 G/A were also higher in the case group than in the control group (all P<0.05). MiRNA-27a rs895819 A/G and Leptin rs7799039 G/A polymorphisms increased the risk of RSA (Exp (B)=2.732, 95% CI=1.625~4.596, P=0.000; Exp (B)=4.081, 95% CI=1.817~9.164, P=0.001). GG-AA or AG-AA carriers had a higher risk of RSA. The miRNA-27a expression of AA carriers of miRNA-27a rs895819 was lower than that of AG+GG carriers both in the case and control groups (all P=0.024). The plasma leptin concentration of GG carriers was lower than that of GA+AA carriers in the case group (P=0.026). CONCLUSIONS The polymorphisms of miRNA-27a rs895819 A/G and Leptin rs7799039 G/A may contribute to an increased risk of RSA.

Topics: Abortion, Habitual; Adult; Base Sequence; Chromatography, High Pressure Liquid; Female; Gene Expression Regulation; Gene Frequency; Genetic Loci; Genetic Predisposition to Disease; Humans; Leptin; Logistic Models; MicroRNAs; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors

To determine whether maternal leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with idiopathic recurrent spontaneous abortion (IRSA).. This case-control association study conducted from 2010 to 2012 at the Department of Gynecology and Obstetrics, University Hospital Center Osijek and Clinical Institute of Medical Genetics Ljubljana included 178 women with a history of three or more IRSAs before the 22nd week of gestation and 145 women with at least two live births and no history of pathologic pregnancies during reproductive period. Polymorphisms of maternal LEP (rs7799039, rs2122627, rs11761556, rs10244329) and LEPR (rs1137101, rs7516341, rs1186403, rs12062820) were assessed by allele specific real-time polymerase chain reaction. Genotype distribution, allele frequencies, and frequency of haplotypes at LEP and LEPR genetic loci were determined.. We observed more frequent genotype for rs7516341 (nominal P=0.034, odds ratio [OR] 0.61, 95% confidence interval [CI] 0.38-0.97) and rs1137101 (nominal P=0.048, OR 1.66, 95% CI 1.00-2.80) in the LEPR gene in patients than in controls, but these results did not remain significant after correction for multiple testing according to Bonferroni (adjusted P value threshold was set at 0.05). We did not observe differential distribution of genotype frequencies in the LEP gene between cases and controls. In patients with IRSA, GTCC haplotype in the LEPR gene locus was significantly less frequent than in controls (PP=0.00865, OR 0.45), contrary to ACTC haplotype (PP=0.0087, OR 1.98).. We showed that genetic variability in the LEPR gene was associated with IRSA, warranting confirmation on a greater number of patients and pathogenesis investigation.

Topics: Abortion, Habitual; Adult; Alleles; Case-Control Studies; Female; Gene Frequency; Genetic Variation; Genotype; Haplotypes; Humans; Leptin; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Pregnancy; Real-Time Polymerase Chain Reaction; Receptors, Leptin; Risk Factors

Recurrent pregnancy loss (RPL) is a common problem during early gestation. The aim of our study was to investigate the association of IL-17 F( rs763780), IL-17 A (rs2275913), and leptin (2548 G/A) gene polymorphisms with RPL in obese and lean Egyptian females, and to find out whether these gene polymorphisms affect the women’s serum levels. One hundred and twenty patients with RPL and 120 fertile volunteers with no history of pregnancy loss were genotyped for leptin (2548 G/A), IL-17 A (rs2275913), and IL-17 F (rs763780) polymorphisms by RFLP. The serum level of IL-17 was measured by ELISA, while serum leptin level was measured by HPLC. We found that IL-17 F (rs763780) polymorphism was associated with a decreased risk of RPL in Egyptian females, and we also found that IL-17 A (rs2275913) and LEP (2548 G/A) SNP were associated with an increased risk of RPL. We also demonstrated that both the IL-17 and leptin levels were elevated in the women with RPL and in an obese subgroup within RPL in comparison to a lean one.

Topics: Abortion, Habitual; Adult; Biomarkers; Case-Control Studies; Egypt; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Interleukin-17; Leptin; Obesity; Polymorphism, Genetic; Pregnancy; Prognosis; Real-Time Polymerase Chain Reaction; Recurrence; Thinness

Leptin signaling is important in the establishment of pregnancy. We sought to determine if single nucleotide polymorphisms (SNPs) in the leptin and leptin receptor genes are associated with idiopathic recurrent pregnancy loss (RPL).. We conducted a case-control study with cases defined as women with idiopathic RPL and controls as parous women without pregnancy losses. A total of 99 cases and 108 controls were genotyped for the leptin (-2548 G/A) SNP and the leptin receptor A223G SNP. Genotype and allele frequencies were compared between cases and controls using χ(2) test.. In this population, there was no significant difference in the genotype or allele frequencies for the leptin (-2548 G/A) or leptin receptor A223G SNPs between women with idiopathic RPL and controls.. Although leptin signaling is critical to many aspects of reproduction, the maternal leptin and leptin receptor SNPs evaluated in this study are unlikely to have a clinically meaningful role in RPL.

Topics: Abortion, Habitual; Adult; Female; Genotype; Humans; Leptin; Polymorphism, Genetic; Pregnancy; Receptors, Leptin

Successful pregnancy is the result of multiple genetic and non-genetic factors. Associations of various SNPs described in this study have not revealed any conclusive results. We have analyzed 47 SNPs using statistical tools like multidimensional regression, classification regression tree, and logistic regression.. Two hundred women with at least three consecutive unexplained spontaneous abortions before 20th week of gestation and 300 control women without any history of recurrent miscarriages (RM) were genotyped using PCR, RFLP and sequencing.. Our results revealed that Leptin 2549 C/A (rs7799039) and TNF-α 238 (rs361525) may play an important role in the maintenance of pregnancy. TNF-α 238 may act as a protective SNP and Leptin 2549 C/A as a susceptible marker among women with RM cases.. Present study demonstrated an association with Leptin 2549C/A (rs7799039) and TNF-α (rs361525) gene polymorphism among RM cases.

Topics: Abortion, Habitual; Female; Genotype; Humans; Leptin; Polymorphism, Single Nucleotide; Regression Analysis; Tumor Necrosis Factor-alpha

The adipokines produced from adipose tissues influence energy homeostasis, resulting in alterations of the adipokine concentrations. This process may be associated with fertility impairment, resulting in recurrent miscarriage. The present study investigated whether there was any association between the UCP2 45-bp indel polymorphism and the adipokine gene polymorphisms, namely leptin 2549 (C/A), adeponectin 276 (G/T) and 45 (T/G) and resistin 420 (C/G) in 200 non-obese recurrent miscarriage patients and 300 ethnically matched negative controls. These markers were studied using gene-specific PCR single specific primer and restriction fragment length polymorphism. For leptin 2549 and adeponectin 276, the A allele and G allele showed 3.42-fold (P=0.0001) and 1.36-fold (P=0.036) increased risk of recurrent miscarriage, respectively. Combined analysis of UCP2 45-bp indel and leptin 2549 showed U0-L0 and U1-L0 variants to be at 2- and 3-fold increased associative risk, respectively. Combined analysis of leptin 2549 and adeponectin 276 showed L0-D0 and L0-D1 variants to be at 2- and 4-fold increased associative risk, respectively. The combination U1-L0-D1-A1-R1 was 4.39-fold higher (P=0.0007) among recurrent miscarriage patients. In conclusion, the results highlight the role of the studied adipokine and UCP2 polymorphisms in recurrent miscarriage among the North Indian non-obese population. Pregnancy invokes a large shift in maternal metabolism. The normal concentrations of adipokines, which maintain the integrity of the hypothalamus-pituitary-gonadal axis, regular ovulatory processes and successful embryo implantation, are altered because of the influence of energy homeostasis, which in turn leads to fertility impairment and recurrent miscarriage of unknown aetiology. Recurrent miscarriage is reported in higher frequency among obese women. The UCP2 45-bp indel polymorphism and the adipokine gene polymorphisms namely leptin 2549 (C/A), adeponectin 276 (G/T), adeponectin 45 (T/G) and resistin 420 (C/G) have been shown to be associated with obesity. Most of the adipokine-related studies done previously have taken into consideration the metabolic function and obesity. However, there exist very few studies to evaluate the role of adipokines in non-obese recurrent miscarriage with no cause of repeated pregnancy losses. The present study focused at evaluating the independent effect of these single-nucleotide polymorphisms in non-obese women undergoing recurrent miscarr

Topics: Abortion, Habitual; Adipokines; Adult; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; Ion Channels; Leptin; Mitochondrial Proteins; Obesity; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Pregnancy; Resistin; Risk Factors; Uncoupling Protein 2

Previous studies in humans and mice have suggested the importance of leptin in fetal growth. Recurrent miscarriage may be a result of abnormal placental and/or fetal development and therefore abnormal leptin levels may be associated with this form of pregnancy loss.. Leptin and leptin-binding activity (LBA) were measured in blood obtained from women who had a history of recurrent miscarriage (n = 53) during weeks 5-6 and 7-8 of pregnancy, and the concentrations were correlated with subsequent pregnancy outcome.. Concentrations of leptin ranged from 1.4-62.8 ng/ml, but there was a strong correlation (r = 0.825, P < 0.001) between leptin values at weeks 5-6 and 7-8 in the same woman. Women who subsequently miscarried had significantly lower plasma leptin concentrations on both weeks 5-6 (13.34 +/- 2.1 ng/ml) (P < 0.05) and 7-8 (13.71 +/- 2.4 ng/ml) (P < 0.01) of pregnancy, than women who subsequently had a term birth (22.04 +/- 2.43 ng/ml week 5-6, 24.76 +/- 3.66 ng/ml week 7-8). LBA values ranged from 1-8.5% but there was no significant difference in LBA in blood obtained from women who subsequently miscarried or had a live birth.. The significantly lower concentrations of leptin in women who subsequently miscarried suggest that leptin may play a role in preventing miscarriage. However, as there was a considerable overlap between the values of leptin in women who subsequently miscarried, and those that had a live birth, these measurements are of limited use in the prediction of pregnancy outcome in these women.

Topics: Abortion, Habitual; Abortion, Spontaneous; Adult; Carrier Proteins; Female; Humans; Labor, Obstetric; Leptin; Osmolar Concentration; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Receptors, Cell Surface; Receptors, Leptin