Impact of Ovarian Sex Steroids on Ovulation and Ovulatory Gene Induction in Aromatase-Null Mice

Female mice deficient in the aromatase gene [aromatase knockout (ArKO)] fail to ovulate owing to an inability to produce estrogens. Here, we demonstrated that sequential administration of adequate amounts of 17β-estradiol (E2), pregnant mare serum gonadotropin, and human chorionic gonadotropin could induce ovulation in immature ArKO mice; nevertheless, significantly fewer oocytes were released into the oviducts in ArKO mice than in wild-type mice. Analysis of ovarian steroids by liquid chromatography coupled with electrospray ionization-tandem mass spectrometry identified a trace amount of E2 in the untreated immature ArKO ovary. The analysis further detected significant increases and decreases in progesterone and testosterone contents, respectively, in addition to an increase of E2 in the ovulation-induced ArKO ovaries compared with the levels in untreated ArKO ovaries. Gene expression analysis demonstrated marked elevation in the mRNA levels of members of the epidermal growth factor family and extracellular matrix-related proteins at 4 h after human chorionic gonadotropin injection in the ovaries of ArKO mice treated for ovulation, as observed in the ovulation-induced wild-type ovaries. Collectively, these findings suggest the vital contribution of the intraovarian milieu of sex steroids to ovulatory regulation in vivo.