The Effect of Hyperinsulinemia on Follicular Function, Ovulation, and Subsequent Oocyte Fertilization and Early Embryonic Quality in a Potential Bovine Model of Polycystic Ovarian Syndrome

The ovarian characteristics of polycystic ovarian syndrome (PCOS) include increased antral follicle count and anovulation. Insulin resistance is highly associated with PCOS, and it was determined to induce insulin resistance to create a new and relevant animal model of PCOS and to determine the effects of hyperinsulinemia on follicular function. In the first experiment, Dexamethasone (DEX) was used to induce hyperinsulinemia and insulin resistance in non-lactating cows. While DEX successfully induced insulin resistance and anovulation, follicles grew to ovulatory size. Further study suggested that the pituitary is capable of releasing a surge of LH in response to GnRH, and follicles are capable of ovulating in response to an LH surge. In contrast, a normal LH surge and ovulation was blocked in 75% of cows administered estradiol, suggesting that DEX is blocking the estradiol-induced positive feedback on the hypothalamus. This model was considered to be very different from PCOS and was abandoned. Growth hormone (GH) is also capable of inducing insulin resistance and this model was pursued to determine if duration of insulin resistance could also be influencing ovarian abnormalities identified in PCOS patients. In this experiment, cows were treated with GH for 4.5 months. Although all cows remained capable of ovulating, those that were treated with the highest dose of GH had increased numbers of antral follicles during the later stages of treatment, characteristic of PCOS. Experiment three analyzed the effect that hyperinsulinemia during antral follicle development has on the oocyte. Propylene glycol was orally administered to induce acute hyperinsulinemia, and FSH was administered to superovulate cows. Resultant structures/embryos were analyzed seven days after ovulation induction. Unexpectedly, there was little effect of treatment on several different parameters of embryo quality. It was interesting, however, to observe that hyperinsulinemia had a profound negative effect on fertilization rates of oocytes, a characteristic also observed in PCOS oocytes. While this work did not create a bovine model completely consistent with PCOS, the increased numbers of follicles and decreased oocyte fertilization rates suggest that hyperinsulinemia and/or insulin resistance may be playing an important role in the follicular and oocyte characteristics observed in PCOS patients.