Developmental Effects of Ethinylestradiol on Reproductive Organs of Female Mice

Abstract

Reproductive organs in female mice are susceptible to exposure to estrogenic substances especially during development. In the present study, C57BL/6J female mice were exposed to the synthetic estrogens ethinylestradiol (EE₂) or diethylstilbestrol (DES), 10-100 or 6.7-67 μg/kg bw, respectively, in utero from day 10 to 18 of pregnancy, and their effects were analyzed at 30 and 40 days of age. Both EE₂ and DES reduced the survival rate of fetuses and newborns in a dose-dependent manner. Polyovular follicles (PF) were found in the ovaries of all groups at 30 days of age including oil-injected controls. However, the incidence of PF was significantly higher in the 50 μg/kg EE₂- and 33.3 μg/kg DES-exposed mice than the control. In vaginal epithelia of the in utero EE₂ exposed, ovariectomized mice, stratification and cornification were encountered even 10 days after ovariectomy. Especially, vaginae in the ovariectomized mice given high dose of EE₂ or DES in utero showed ovary-independent proliferation of the epithelium. Thus, it is clear that prenatal exposure to EE₂ or DES induces reproductive abnormalities, including PF, ovary-independent vaginal epithelial stratification and cornification.