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

Abstract

We investigated the delayed effects of neonatal exposure to 17α-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 μg/kg) within 24h 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 μg/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 μg/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.

• Authors: Miwa Takahashi, Kaoru Inoue, Tomomi Morikawa, Saori Matsuo, Seigo Hayashi, Kei Tamura, Gen Watanabe, Kazuyoshi Taya, Midori Yoshida
• Journal: Reproductive toxicology (Elmsford, N.Y.) (Reprod Toxicol) Vol. 40 Pg. 16-23 (Sep 2013) ISSN: 1873-1708 [Electronic] United States
• PMID: 23707403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Carcinogens
• Estrogens
• Methylnitronitrosoguanidine
• Ethinyl Estradiol
• ENNG
• Progesterone
• Estradiol

Topics

• Adenocarcinoma (blood, chemically induced, pathology)
• Animals
• Anovulation (blood, chemically induced, pathology)
• Carcinogens
• Estradiol (blood)
• Estrogens (toxicity)
• Estrous Cycle (drug effects)
• Ethinyl Estradiol (toxicity)
• Female
• Hyperplasia (blood, chemically induced, pathology)
• Mammary Glands, Animal (drug effects, pathology)
• Methylnitronitrosoguanidine (analogs & derivatives)
• Organ Size (drug effects)
• Pregnancy
• Prenatal Exposure Delayed Effects
• Progesterone (blood)
• Rats
• Rats, Wistar
• Uterine Neoplasms (blood, chemically induced, pathology)
• Uterus (drug effects, pathology)
• Vagina (drug effects, growth & development)