Exposing cultured mouse ovarian follicles under increased gonadotropin tonus to aromatizable androgens influences the steroid balance and reduces oocyte meiotic capacity

Abstract

Acquisition of oocyte developmental competence relies on the well-controlled events accompanying antral follicular development. Elevated basal androgen levels, as in PCOS, potentially affect oocyte quality. Current experiments in an in vitro follicle bioassay studied dose-effects of androstenedione and testosterone on FSH and hCG stimulated antral follicle growth and meiotic maturation. The addition of either androgens altered follicle's endogenous production of androstenedione, testosterone, estradiol, and progesterone and affected the oocyte's capacity to resume meiosis. Exposure to 200nM androstenedione induced an increased production of testosterone and estradiol. Exposure to a concentration of ≥200nM testosterone induced elevated levels of estradiol and progesterone. Significant dose-dependent negative effects on polar body extrusion were seen at concentrations of ≥200nM of either androgen. In addition, chromosome displacement on the metaphase plate was observed in oocytes obtained from androstenedione-treated follicles. Follicles exposed to a combination of 25mIU/ml FSH and 3mIU/ml hCG and elevated aromatizable androgens altered the steroid production profile, affected the follicular development and impaired oocyte meiotic competence.