Effects of neonatal exposure to the antiprogestin mifepristone, RU 486, on the sexual development of the rat

Abstract

RU 38486 (RU 486, mifepristone) is a potent progesterone receptor antagonist that has been used in humans in the pharmacologic induction of abortion. The effects of exposure to RU 486 during the neonatal period of the rat has not been previously reported. We examined the consequences of such exposure in the context of sexual development. Long-Evans rat pups were subcutaneously injected with either 100 μg RU 486, 300 μg RU 486, 500 μg progesterone (P), or 50 μg testosterone propionate (TP) in 0.05 ml sesame oil, or oil vehicle alone within 8 hours of birth, and 24 and 48 hours later. Treatment with either dose of RU 486 significantly advanced the onset of vaginal opening in females and attenuated defeminization of the lordosis response measured in males castrated as adults. As expected, TP-treated subjects were masculinized and defeminized, with females displaying fused vaginas and neither males nor females demonstrating lordosis behavior. Treatment with P caused no significant alterations in either the timing of vaginal opening or sexual behavior. These results indicate that RU 486 has clear developmental effects in the rat. Since this may well be a result of progesterone receptor blockade, further research is needed to clarify the processes involved.