REPRODUCTIVE FUNCTION IN RATS AFTER MIFEPRISTONE-INDUCED TERMINATION OF PREGNANCY

The effect of mifepristone, a potent progesterone receptor antagonist, on the reproductive function during early pregnancy in rats was exami ned. A single dose of this drug (10 mg/kg) was injected s.c. at 1200 h on day 4 (Group I), day 7 (Group Il) or day 10 (Group III) of pregnan cy. Gestation was interrupted and the vaginal cytology showed a typica l proestrus condition two days after mifepristone treatment in all the groups. When compared with cycling proestrus rats, serum LH concentra tions at 1800 h in the mifepristone-induced proestrus were lower in Gr oup I, similar in Group II and higher in Group III, and serum prolacti n (PRL) values were lower in Group I, but not different in Groups II a nd III. Serum progesterone levels were higher in the three experimenta l groups when compared with cycling proestrus rats, and similar to tha t of pregnant rats. Rats in Group I showed a significantly lower sexua l 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 pre gnant and showed a delayed pseudopregnancy-like condition. These resul ts indicate that mifepristone administered in a single dose to early p regnant rats terminates pregnancy and induces a proestrus condition tw o days after treatment followed by successful postovulatory contracept ion. The mifepristone-induced proestrus is characterized by a differen tial pattern of serum LH, PRL and progesterone concentrations, mating behavior and ovulation rates, depending on the day of pregnancy when m ifepristone is administered.