Gonadotropin induction of ovulation and corpus luteum formation in young estrogen receptor-alpha knockout mice

Estrogen receptor-alpha (ER-alpha) knockout (ER alpha KO) female mice are i nfertile. Initially, they exhibit normal follicular development, but by 4-5 wk of age, they begin to develop hemorrhagic ovarian cysts. Follicles in a dult ERaKO female mice progress to the graafian stage, but there are no cor pora lutea (CL). To test whether ER alpha is required for ovarian folliculo genesis, ovulation, and CL formation, eCC and hCG were used to ovulate 3- t o 5-wk-old ER alpha KO and wildtype (WT) sibling mice. Gonadotropin adminis tration resulted in ovulation in both ER alpha KO and WT mice. Gonadotropin -treated ER alpha KO females that ovulated produced 7.09 +/- 0.77 oocytes p er mouse, whereas gonadotropin-treated WT female mice had 16.17 +/- 0.84 oo cytes. Surprisingly, ruptured ER alpha KO ovarian follicles developed into CL that had normal morphology. Gonadotropin-treated ERaKO mice had 3-fold h igher concentrations of serum progesterone than did control ER alpha KO mic e that had been administered saline rather than gonadotropins. Thus, the CL in gonadotropin-treated ER alpha KO mice appeared to be steroidogenically functional. On the basis of these findings, ovarian folliculogenesis, ovula tion, and CL formation can occur in the absence of ER alpha, although to a lesser extent than in WT mice.