TRANSPLACENTAL EFFECT OF ETHINYL ESTRADIOL ON MOUSE VAGINAL EPITHELIUM

The effect of prenatal administration of ethinyl estradiol (EE) on the vaginal epithelium of adult mice was examined histologically. The mice were the offspring of JCL/ICR strain mice given orally 0.02 mg/kg body weight/day or 0.01 mg/kg/day of EE dissolved in olive oil from day 11 to day 17 of gestation at a stage when the urogenital sinus has just appeared in the embryos. The control mice were offspring of those fed with the vehicle alone. Autopsies were performed at 10 to 14 weeks of age. Another group of mice exposed to 0.02 mg/kg/day of EE or vehicle alone in utero, were spayed at 16 weeks of age and killed at 32 weeks of age. In the experimental nonspayed mice, hyperplasia of the vaginal epithelium with intense cornification was seen. The epithelium was significantly thicker than in the controls and showed an EE dose-response relation. One of the 16 mice exposed to 0.01 mg/kg/day of EE in utero had cystic or gland-like structures in the stroma and mucus-secreting cells in the surface epithelium consisting of columnar cells. In some experimental spayed mice, vaginal hyperplasia with cornified epithelium and hypertrophy of the ovarian interstitial tissue without corpus luteum were seen. These results indicate that EE can cross fetal membranes and affect undifferentiated cells in the urogenital sinus and/or Müllerian epithelium.