Journal
REPRODUCTIVE TOXICOLOGY
Volume 40, Issue -, Pages 16-23Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2013.05.005
Keywords
17Alpha-ethynylestradiol; Neonatal exposure; Delayed effects; Estrous cycle; Uterine carcinogenesis
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Funding
- Health and Labor Sciences Research Grants, Research on Risk of Chemical Substances, Ministry of Health, Labor and Welfare, Japan [H22-Toxicol-003]
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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.
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