Gonadotropin Induction of Ovulation and Corpus Luteum Formation in Young Estrogen Receptor-α Knockout Mice1

Estrogen receptor-α (ERα) knockout (ERαKO) female mice are infertile. Initially, they exhibit normal follicular development, but by 4–5 wk of age, they begin to develop hemorrhagic ovarian cysts. Follicles in adult ERαKO female mice progress to the graafian stage, but there are no corpora lutea (CL). To test whether ERα is required for ovarian folliculogenesis, ovulation, and CL formation, eCG and hCG were used to ovulate 3- to 5-wk-old ERαKO and wild-type (WT) sibling mice. Gonadotropin administration resulted in ovulation in both ERαKO and WT mice. Gonadotropin-treated ERαKO females that ovulated produced 7.09 ± 0.77 oocytes per mouse, whereas gonadotropin-treated WT female mice had 16.17 ± 0.84 oocytes. Surprisingly, ruptured ERαKO ovarian follicles developed into CL that had normal morphology. Gonadotropin-treated ERαKO mice had 3-fold higher concentrations of serum progesterone than did control ERαKO mice that had been administered saline rather than gonadotropins. Thus, the CL in gonadotropin-treated ERαKO mice appeared to be steroidogenically functional. On the basis of these findings, ovarian folliculogenesis, ovulation, and CL formation can occur in the absence of ERα, although to a lesser extent than in WT mice.