leptin and Ovarian-Diseases

Anovulatory infertility affects a large proportion of reproductive-aged women. Major improvements in successful clinical treatment of this prevalent disorder in women's health have been made possible because of biomedical research employing nonhuman primates. Experiments on female rhesus monkeys were the first to demonstrate that the key hypothalamic neurotransmitter, gonadotropin-releasing hormone, involved in stimulating pituitary gonadotropin synthesis, storage, and release was bioactive only when released in approximately hourly bursts. This breakthrough in understanding gonadotropin regulation enabled identification of hypogonadotropic, apparently normogonadotropic, and hypergonadotropic forms of anovulatory infertility, and development of appropriate stimulatory or inhibitory gonadotropin therapies. Treatments to overcome anovulatory infertility represent one of the major advances in clinical reproductive endocrinology during the last 25 yr. The future promise of nonhuman primate models for human ovulatory dysfunction, however, may be based on an increased understanding of molecular and physiological mechanisms responsible for fetal programming of adult metabolic and reproductive defects and for obesity-related, hyperinsulinemic impairment of oocyte development.

Topics: Animals; Anovulation; Disease Models, Animal; Female; Gonadotropin-Releasing Hormone; Humans; Hyperprolactinemia; Hypothalamus; Infertility, Female; Leptin; Ovarian Diseases; Primates; Stress, Physiological; Time Factors

In mammals, triacylglycerol (TAG) accumulation in nonadipose tissue, termed lipotoxicity, develops with obesity and can provoke insulin resistance, overt diabetes, and ovarian dysfunction. Leptin, an adipose tissue hormone, may mediate these effects. Feed-satiated broiler breeder hens manifest lipotoxicity-like symptoms. Changes in body and organ weights, hepatic and plasma TAG, nonesterified fatty acids (NEFA), ovarian morphology, and egg production in response to acute voluntary increases of feed intake were measured in 2 studies with Cobb 500 broiler breeder hens provided with either 145 or > or = 290 g of feed/d per hen for 10 d. In both studies, no hen fed 145 g of feed/d exhibited ovarian abnormalities, whereas approximately 50% of feed-satiated hens did. Egg production in feed-satiated hens was reduced from 73.3 to 55.8% (P = 0.001). Morphology indicated that apoptosis-induced atresia occurred in the hierarchical follicles. Fractional weight of yolk increased from 29.3 to 30.6% (P = 0.016) and no longer correlated to egg weight. Body, liver, and abdominal adipose weights were significantly greater (P < 0.05) in feed-satiated hens, as were plasma concentrations of glucose, NEFA, TAG, insulin, and leptin (P < 0.05). Feed-satiated hens with abnormal ovaries had significantly more liver and abdominal fat, greater plasma leptin and TAG concentrations, and more saturated fatty acids in plasma NEFA than did feed-satiated hens with normal ovaries. Differences in severity of lipotoxic metabolic and hormonal responses among feed-satiated hens were closely linked to the incidence of ovarian abnormalities and granulosa cell susceptibility to apoptosis and necrosis.

Topics: Adiposity; Animal Feed; Animals; Apoptosis; Blood Glucose; Egg Yolk; Female; Insulin; Leptin; Lipid Metabolism; Lipids; Liver; Ovarian Diseases; Ovary; Oviposition; Poultry Diseases; Triglycerides; Weight Gain

The purpose of the present study was to determine whether excessive body fat and altered metabolic hormone concentrations in the circulation were associated with ovarian acyclicity in the world's largest land mammal, the African elephant. We compared body condition, glucose, insulin and leptin concentrations and the glucose-to-insulin ratio (G:I) between cycling (n=23; normal 14-16 week cycles based on serum progestagens for at least 2 years) and non-cycling (n=23; consistent baseline progestagen concentrations for at least 2 years) females. A validated body condition score (BCS) index (five-point scale; 1=thinnest, 5=fattest) was used to assess the degree of fatness of the study elephants. The mean BCS of non-cycling elephants was higher than that of their cycling counterparts. There were differences in concentrations of serum metabolic biomarkers, with non-cycling elephants in the BCS 5 category having higher leptin and insulin concentrations and a lower G:I ratio than cycling BCS 5 females. Using 'non-cycling' as the outcome variable in regression models, high BCS was a strong predictor of a non-cycling status. This study provides the first evidence that ovarian acyclicity in zoo African elephants is associated with body condition indicative of obesity, as well as elevated, perturbed biomarkers of metabolic status.

Topics: Adiposity; Animals; Animals, Zoo; Biomarkers; Blood Glucose; Elephants; Estrous Cycle; Female; Insulin; Leptin; Obesity; Ovarian Diseases; Ovary; Reproduction; Up-Regulation

This study was designed to investigate leptin levels in the fluid in ovarian endometriomas (OEs) and to compare the expression of leptin and its receptors (OBR) in ovarian tissue affected by endometrioma in infertile women to its expression in the normal ovarian tissue of fertile controls without endometriosis.. In this case-control observational study, ovarian tissue, blood samples and peritoneal fluid were obtained from 20 women (10 fertile controls without endometriosis or any ovarian disease, who were undergoing tubal ligation surgery, and 10 infertile women with severe endometriosis and OE). The ovarian endometriomal fluid (EF) was aspirated, and peritoneal-implant (PI) biopsies were performed. The tissues removed during the surgeries were immediately frozen in liquid nitrogen to determine expression levels by western blot and leptin levels by ELISA.. OBR was expressed at higher levels in the ovarian tissue affected by endometrioma than in the normal ovarian tissue (control = 0.38 ± 0.05, study = 0.60 ± 0.09, p = 0.03), but there was no significant difference in leptin levels between these groups (control = 0.57 ± 0.1, study = 0.35 ± 0.1, p = 0.18). Positive and significant correlations were observed between leptin and OBR in the OE (r = 0.85, p = 0.004) and in the PI (r = 0.87, p = 0.001). ELISA results demonstrate a greater leptin concentration within the EF compared with the serum and the PF (serum = 14.25 ± 1.63, PF = 5.98 ± 2.0, EF = 73.8 ± 16.2, p = 0.0001), but there was no correlation between these variables. A positive, significant and strong correlation was observed between PF leptin levels and the expression of leptin and OBR in PI (leptin: r = 0.78, p = 0.007/OBR: r = 0.68, p = 0.04) and between the EF leptin levels and the expression of leptin and OBR in the OE (leptin: r = 0.88, p = 0.008/OBR: r = 0.89, p = 0.005).. These data suggest that leptin may play an important role in the physiopathology of OE through a modulatory interaction with its active receptor.

Topics: Adult; Ascitic Fluid; Case-Control Studies; Endometriosis; Female; Humans; Infertility, Female; Leptin; Ovarian Diseases; Ovary; Receptors, Leptin; Up-Regulation

Pelvic endometriosis is a chronic inflammatory disease with an immunological background. Yet there is paucity of contemporary research exploring both the angiogenic cytokines, leptin and IL-8 for a possible role in its pathophysiology.. To compare levels of both leptin and IL-8 in peritoneal fluid (PF) in women with endometriosis vs. fertile controls and correlate with disease stage, type and symptoms.. PF from 58 women with endometriosis and 28 women undergoing tubal ligation was collected at laparoscopy and leptin and IL-8 levels were measured using ELISA. Results showed significantly higher levels of both cytokines in women with endometriosis. Significantly higher leptin and IL-8 levels were demonstrated in patients with early peritoneal (ASRM stage I and II) and advancing disease (ASRM stage III and IV), respectively. Levels of leptin/IL-8 were significantly lower in patients with endometrioma (4.8 ng/mL/32 pg/mL) vs. implants (13.0 ng/mL/68 pg/mL). There was no correlation of infertility or chronic pelvic pain with these levels.. Both leptin and IL-8 levels are raised in PF of women with endometriosis reflecting inflammation and dysregulated immunomodulation. Higher levels of leptin were seen in early stages; IL-8 seems to stimulate the disease in a dose-dependent manner.

Topics: Adult; Ascitic Fluid; Case-Control Studies; Endometriosis; Female; Humans; Infertility, Female; Interleukin-8; Leptin; Ovarian Diseases; Pelvic Pain; Peritoneal Diseases

Some studies have suggested a possible role of leptin, an active cytokine produced by adipocytes, in the pathogenesis of pelvic endometriosis. The present study was designed to assess leptin levels in the peritoneal fluid (PF) of women with the 'deep' or 'superficial' types of ovarian endometriosis. Twenty-seven women with a single ovarian endometrioma having a mean diameter between 3 and 5 cm were included in the study. Patients were divided into two groups according to the type of ovarian endometriosis: Group A (n = 11) consisted of women with 'superficial' endometriomas located at the ovarian surface; Group B (n = 16) included patients with 'deep' intra-ovarian endometriomas. Women undergoing laparoscopy for unexplained infertility and not affected by pelvic and/or ovarian endometriosis were considered as controls (Group C, n = 10). Patients with an ovarian endometrioma had significantly increased PF leptin concentrations than endometriosis-free controls (Groups A and B vs. Group C, p < 0.01). Patients with 'superficial' endometriomas had significantly higher PF leptin levels compared with patients with 'deep' endometriomas (Group A vs. B, p < 0.01). This difference remained significant after correction for the BMI; moreover, a positive correlation between PF leptin and BMI was observed in Groups B and C, but not in women with 'superficial' endometrioma (Group A). Our observations suggest that: (a) leptin could play an active role in promoting the development of 'superficial' ovarian endometriomas and (b) 'superficial' and 'deep' ovarian endometriomas could have a different pathogenesis.

Topics: Analysis of Variance; Ascitic Fluid; Endometriosis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Ovarian Diseases; Ovary; Patient Selection; Regression Analysis

This study was designed to measure leptin concentrations in the peritoneal fluid (PF) of women with different aspects of pelvic endometriosis. Among 36 consecutive women undergoing laparoscopy, nine were diagnosed as having minimal-mild endometriosis (stage I-II). Among nine other subjects with advanced stage (III-IV) disease, six showed one or more ovarian endometriotic cysts as the only operative finding. The remaining 18 unaffected women constituted the control group. Patients with endometriosis had significantly higher PF leptin concentrations (32.6 +/- 16.2 versus 17.1 +/- 6.6 ng/ml, P = 0.002); this difference remained significant when corrected for body mass index (BMI) (PF leptin/BMI ratio 1.41 +/- 0.67 versus 0.76 +/- 0.28, P = 0.001). Furthermore, the PF leptin/BMI ratio was significantly higher in women with peritoneal implants than in those in whom no implant was found at laparoscopy (1.6 +/- 0.7 versus 0.83 +/- 0.33, P = 0.007). Conversely, patients with one or more ovarian endometriomata as the only finding, had a PF leptin/BMI ratio comparable with that in women where no cyst was found (1.05 +/- 0.4 versus 1.1 +/- 0.65). In women with stage I-II endometriosis, a higher mean PF leptin/BMI ratio was found compared with those affected by stage III-IV (1.78 +/- 0.68 versus 1.05 +/- 0.43, P = 0.01). These results show that during endometriosis the presence of peritoneal disease, and not of ovarian endometriotic cysts, influences leptin concentrations in PF. The data suggest that leptin may play a role in the development of peritoneal endometriosis, and that different biochemical phenomena might be involved in the pathogenesis of the ovarian form of the disease.

Topics: Adult; Ascitic Fluid; Body Mass Index; Endometriosis; Female; Humans; Laparoscopy; Leptin; Ovarian Diseases; Peritoneal Diseases; Regression Analysis