Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared with Moderate-Weight Women

Context: Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period. Objective: This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence. Design, Setting, and Participants: Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33; BMI 20-24.9 kg/m(2)), overweight (n = 31; BMI 25-29.9 kg/m(2)), and obese (n = 32; BMI >= 30 kg/m(2)). Intervention: For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes. Main Outcome Measures: Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance. Results: Increasing BMI was associated with increased follicular fluid insulin (P < 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P < 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women. Conclusions: Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients. (J Clin Endocrinol Metab 94: 1533-1540, 2009)