Obesity Disrupts Ovarian Vasculature and Hemodynamics during the Preovulatory Period

Ovulation failure accounts for over 25% of infertility cases in reproductive-age women in the U.S., with obese women three times more likely to experience anovulatory infertility. The mechanisms by which obesity impairs ovulation remain unclear. The preovulatory luteinizing hormone (LH) surge induces changes in ovarian vasculature crucial for ovulation. We hypothesized that obesity disrupts ovarian vascular function, contributing to impaired ovulation. Using color Doppler ultrasonography, we assessed ovarian vessel hemodynamics in control mice and two obese groups: high-fat diet (HFD) and Agouti viable Yellow (AvY) mice. Both obese groups had reduced ovulation rates following superovulation treatment. In control mice, flow velocities in the ovarian artery, medullary, and cortical vessels increased within the first hour following human chorionic gonadotropin (hCG) treatment, while velocities remained constant in obese mice. This change in velocity correlated with ovulation rates, indicating its importance for ovulation success. Analysis of the overall ovarian vasculature through lectin labeling revealed an increased presence of capillaries in HFD ovaries. Transcriptomic analysis of granulosa cells and ovarian stroma at 0 h post-hCG identified differentially expressed genes involved in vascular development, extracellular matrix (ECM) organization, and inflammation, crucial processes for vascular function and ovulation. This study characterizes for the first time in vivo ovarian hemodynamics in adult mice, showing that the LH surge-induced blood flow increase is disrupted in obese mice. These disturbances are linked to altered vascular regulators and abnormal vessel structure, suggesting that improving blood flow could be a therapeutic target for enhancing ovulation in obese women.