Reproductive function in rats after mifepristone-induced termination of pregnancy

Abstract

The effect of mifepristone, a potent progesterone receptor antagonist, on the reproductive function during early pregnancy in rats was examined. A single dose of this drug (10 mg/kg) was injected s.c. at 1200 h on day 4 (Group I), day 7 (Group II) or day 10 (Group III) of pregnancy. Gestation was interrupted and the vaginal cytology showed a typical proestrus condition two days after mifepristone treatment in all the groups. When compared with cycling proestrus rats, serum LH concentrations at 1800 h in the mifepristone-induced proestrus were lower in Group I, similar in Group II and higher in Group III, and serum prolactin (PRL) values were lower in Group I, but not different in Groups II and III. Serum progesterone levels were higher in the three experimental groups when compared with cycling proestrus rats, and similar to that of pregnant rats. Rats in Group I showed a significantly lower sexual receptivity and ovulation rate when compared with Groups II and III or cycling proestrus rats. Most of the mifepristone-treated rats that copulated during the night of the induced proestrus did not become pregnant and showed a delayed pseudopregnancy-like condition. These results indicate that mifepristone administered in a single dose to early pregnant rats terminates pregnancy and induces a proestrus condition two days after treatment followed by successful postovulatory contraception. The mifepristone-induced proestrus is characterized by a differential pattern of serum LH, PRL and progesterone concentrations, mating behavior and ovulation rates, depending on the day of pregnancy when mifepristone is administered.