Delayed effects of neonatal exposure to 17alpha-ethynylestradiol on the estrous cycle and uterine carcinogenesis in Wistar Hannover GALAS rats

We investigated the delayed effects of neonatal exposure to 17 alpha-ethynylestradiol (EE) on the female reproductive tract using Wistar Hannover GALAS rats. Female pups received single injections of EE (0, 0.02, 0.2, 2, 20, or 200 mu g/kg) within 24 h after birth and estrous cyclicity was observed until 10 months of age. All animals were treated at 9 weeks of age with the uterine carcinogen, N-ethyl-N'-nitro-N-nitrosoguanidine. Although the vaginal opening was not affected, abnormal cycles were significantly increased from 0.2 mu g/kg. Persistent estrus was prominent and the incidence increased age- and dose-dependently. Severity of atypical hyperplasia of the uterus tended to increase from 2 mu g/kg. In these groups, serum progesterone level was lowered relative to estradiol level. In conclusion, estrous cyclicity was a sensitive indicator reflecting delayed effects on the female reproductive tract. Early onset of anovulation leading to prolonged estrogen exposure might be a risk factor for uterine carcinogenesis. (C) 2013 Elsevier Inc. All rights reserved.