Elucidating the impact of obesity on hormonal and metabolic perturbations in polycystic ovary syndrome phenotypes in Indian women.

Polycystic ovary syndrome is a complex endocrinopathy with heterogeneous presentation and multifactorial etiology. We have undertaken this case-control study to compare metabolic and endocrine characteristics in different phenotypic subgroups of women with PCOS and the impact of obesity on them. Women with PCOS (n = 489) were classified into 4 phenotypes according to Rotterdam criteria. Comparisons of clinical, biochemical and hormonal parameters were performed across all phenotypic groups of PCOS and with controls (n = 270) by Welch's ANOVA with subsequent Games-Howell post-hoc test. We found maximum prevalence of normoandrogenic phenotype D, which is milder form of PCOS in terms of insulin resistance, gonadotropin levels and dyslipidemia, followed by phenotype A, in our total study population. After classification of the study group into lean and obese groups, only few insulin and lipid-related traits showed marked differences between phenotypes. Further, we noted that obese women showed adverse metabolic but not androgenic traits compared to lean counterparts in the same phenotype. Metabolic syndrome frequency is increased in hyperandrogenic phenotypes with HDL-C and waist circumference being most predominant contributing factors in total, lean and obese groups. We demonstrate that in our study population there is greater occurrence of phenotype D of PCOS. Our study highlights the importance of clinicians concurrently employing Rotterdam criteria along with obesity status for ascertaining accurate PCOS status and formulating suitable therapeutic intervention

Estrogenized mouse model of polycystic ovary highlights mitochondrial pathway of apoptosis

293-304Polycystic ovary syndrome, which is a major cause of anovulatory infertility in women, featured by an ovarian morphology that reflects arrested follicular growth and accumulation of cystic follicles. Alteration of apoptotic process may promote development and persistence of follicular cysts, which has not been explored in details. Female animals exposed to estrogenic compounds at specific growth stages show altered pubertal maturation, ovulatory dysfunction, accumulation of follicular cysts and infertility. Here, we developed a mouse model of cystic ovary by neonatal estrogenization and investigated apoptotic changes underlying cystogenesis across various time points. We compared pro- and anti-apoptotic markers along with ovarian morphology between control and estradiol treated mice using several techniques including flow cytometry, immunohistochemistry and electron microscopy. Treated mice presented with cystic follicles with degenerated oocyte and reduced granulosa cell layer, anovulation, along with persistent estrus cycle and infertility. Increased apoptosis was demonstrated in cystic follicles with significantly increased expression of JC-1, Bid, caspase-9 and caspase-3. Thus, our findings highlight the involvement of mitochondrial pathway of apoptosis in development of polycystic ovary in response to neonatal exposure to estrogen. This model may serve to delineate the effect of environmental estrogen exposure to altered ovarian physiology which is frequently observed in PCOS women