Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice

Objective: To evaluate antidiabetic and anti-inflammatory effects of resveratrol on the ovarian response to controlled ovarian hyperstimulation (COH) in obesity-related infertility. Design: Experimental. Setting: University laboratory. Animal(s): Sixteen female ob/ob mice and 16 female C57BL/6J mice undergoing COH. Intervention(s): Wild-type placebo group; wild-type resveratrol group; ob/ob mice placebo group; ob/ob mice resveratrol group. Resveratrol 3.75 mg/kg daily for 20 days and undergoing COH protocol. Main Outcome Measure(s): Body and reproductive system weight, food intake, fasting blood glucose, plasma insulin and T levels, and Homeostatic Index of Insulin Resistance; interleukin-6 and tumor necrosis factor-alpha levels in adipose tissue by Westena blot; assessment of quality and quantity of oocytes retrieved; and quantitative analysis of ovarian follicles. Result(s): Plasma insulin and T levels decreased and Homeostatic Index of Resistance improved in ob/ob mice treated with resveratrol. Interleukin-6 and tumor necrosis factor-alpha levels were significantly reverted back to near normalcy after resveratrol treatment in obese mice. Administration of resveratrol resulted in a significantly higher number of oocytes collected in wild-type mice. The number of primary, growing, preovulatory, and atretic follicles was found to be decreased in the group of obese mice treated with resveratrol when compared with the obese control group. Conclusion(s): Resveratrol administration could exert benefits against loss of ovarian follicles, and these actions may be mediated, at least in part, via anti-inflammatory, insulin-sensitizing, and antihyperandrogenism effects. These observations further validate the therapeutic potential of resveratrol to preserve ovarian reserve in conditions associated with obesity. Our results suggest the possible clinical use of resveratrol to enhance the ovarian response to COH in normal-weight females. (C) 2015 by American Society for Reproductive Medicine.