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), overweight (n = 31; BMI 25-29.9 kg/m), and obese (n =32; BMI ≥30 kg/m). Intervention: For each patient, follicular fluidwasrecoveredfromsingle 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