Reproductive effects of prenatal exposure to 5-bromo-2'-deoxyuridine on male rats

5-Bromo-2'-deoxyuridine (BrdU) was administered intraperitoneally to Sprague-Dawley rats at doses of 12.5, 25, 50, or 100 mg/kg/d on days 9 through 15 of gestation, and at 50 or 100 mg/kg/d on days 16 through 20 of gestation. Dams were allowed to deliver naturally and the numbers of live and dead pups were recorded. Male offspring were allowed to mature and then cohabited with untreated female rats for assessment of reproductive performance. Dam body weight gain during pregnancy and lactation periods was not reduced by the treatment with BrdU. Dams treated with 50 and 100 mg BrdU/kg on days 9 through 15 of gestation had litters with decreased survival rates. The male offspring from dams treated with 25, 50, and 100 mg BrdU/kg on days 9 through 15 of gestation had reduced body weights over the course of the entire study. A dose-related decrease in copulation and fertility rates was found in the male offspring of dams treated on days 9 through 15 of gestation, while no significant decrease in those rates were found in the male offspring of dams treated on days 16 through 20 of gestation. Neither histopathologic examination of testes nor sperm examination indicated the cause of the impaired fertility in the male offspring from dams treated with BrdU on days 9 through 15 of gestation. All of the male offspring of dams treated with 100 mg BrdU/kg on days 9 through 15 of gestation failed to copulate, and some of the male offspring of dams treated with 50 mg BrdU/kg on days 9 through 15 of gestation did not form copulatory plugs or formed very small plugs. Dilatation of the lateral ventricles and cysts in the pars distalis of the pituitary were observed in all of the male offspring of dams treated with 100 mg BrdU/kg on days 9 through 15 of gestation. The impaired fertility of the male offspring of dams treated prenatally with BrdU may have resulted from BrdU exposure effects on central nervous system action such as loss of libido and from failure to form proper copulatory plugs, rather than the direct effects of BrdU on the male reproductive organs.