Effects of treatment of male and female rats in infancy with mifepristone on reproductive function in adulthood

Abstract

Treatment of neonatal male and female rats with mifepristone (1 mg s.c. every 2 days from Day 1 to 15 or Day 4 to 18 of life) interfered with the normal development of their reproductive capacities and of the adrenal glands. The effect on the adrenal glands seemed only temporary. Effects on reproductive functions seemed permanent. Female rats developed abnormalities in structure of the oviduct and ovarian capsule reminiscent of effects reported after perinatal treatment with androgen or oestrogen. During adulthood, anovulatory polyfollicular ovaries developed, reminiscent of rats treated with a small dose of androgen in infancy. Males showed retardation of testicular growth and delay of puberty. During adulthood testes did not grow beyond 65% that of normal rats. Sexual behaviour was deficient in that ejaculations occurred only rarely; when ejaculations did occur, fertility was unimpaired. Males treated with mifepristone in infancy exhibited female sexual behaviour as adults after castration and injections of testosterone and oestradiol. All effects pointed to an insufficient action of testicular hormones in infancy to bring about normal 'masculinization'. Mifepristone therefore appears to show 'teratogenic' actions in rats which affect female reproductive tract development and, in males and females, development of the systems underlying normal reproductive activity and functions in adulthood.