Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring

The objective of this study was to examine the effects of maternal exposure to xenoestrogen, at levels comparable to or greater than human exposure, on development of the reproductive tract and mammary glands in female CD-I mouse offspring. Effects of genistein (GEN), resveratrol (RES), zearalenone (ZEA), bisphenol A (BPA) and diethylstilbestrol (DES) were examined. Beginning on gestational day 15, pregnant CD-1 mice were administered four daily subcutaneous injections with 0.5 or 10 mg/kg/day of GEN, RES, ZEA or BPA, 0.5 or 10 mug/kg/day of DES dissolved in dimethylsulfoxide (DMSO), or DMSO vehicle (n = 6). Vaginal opening was monitored, 6 animals per group were autopsied at 4, 8, 12 and 16 weeks of age and estrous cyclicity was monitored from 9 to I I weeks of age. Maternal exposure to xenoestrogen accelerated puberty onset (vaginal opening) and increased the length of the estrous cycle; mice treated with GEN, RES, BPA or DES spent more time in diestrus, and ZEA-treated mice spent more time in estrus. Lack of corpora lutea and vaginal cornification were observed at 4 weeks of age in the high-dose GEN (33%) and RES (17%) groups, and in the high- and low-dose BPA groups (33 and 50%, respectively) and DES groups (83 and 100%, respectively). Lack of corpora lutea and vaginal cornification was observed in the high-dose ZEA group at 4, 8, 12 and 16 weeks of age (83, 100, 83 and 33%, respectively). Mammary gland differentiation was accelerated in ZEA-and BPA-treated mice with corpora lutea at 4 weeks of age. ZEA-treated mice without corpora lutea showed mammary growth arrest at 8, 12 and 16 weeks of age; their mammary glands consisted only of a dilatated duct filled with secreted fluid. Mammary gland growth was similar with xenoestrogens other than ZEA or BPA to that of the controls at all time points. High-dose GEN and RES and high- and low-dose BPA and DES exerted transient effects on the reproductive tract and mammary glands, whereas ZEA exerted prolonged effects. (C) 2004 Elsevier Inc. All rights reserved.