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Exposure to ethinyl estradiol prenatally and/or after sexual maturity induces endometriotic and precancerous lesions in uteri and ovaries of mice
Author(s) -
Koike Eiji,
Yasuda Yoshiko,
Shiota Mitsuru,
Shimaoka Masao,
Tsuritani Mitsuhiro,
Konishi Hiroyoshi,
Yamasaki Harufumi,
Okumoto Katsumi,
Hoshiai Hiroshi
Publication year - 2013
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/j.1741-4520.2012.00383.x
Subject(s) - endocrinology , medicine , offspring , aromatase , estrogen , adenomyosis , ovary , endometriosis , andrology , biology , pregnancy , cancer , breast cancer , genetics
Unrecognizable exposure to estrogenic substance may cause estrogen‐dependent diseases, endometriosis and cancer. Pregnant mice ( ICR / J cl, CLEA ) were exposed to 0.01 mg ethinyl estradiol ( EE 2 )/kg per day or vehicle (olive oil) through oral intubation from day 11 to 17 of gestation. They delivered their offspring and raised them. When the experimental female F 1 mice were at 8 weeks of age, they were not exposed to EE 2 or to the same dose of EE 2 or to vehicle twice a week until 20 weeks of age. The control female F 1 mice were exposed to the same dose of EE 2 or vehicle alone, similarly. All mice were killed at 28 weeks of age. The resected uteri and ovaries were processed for microscopic examinations and for determination of the aromatase m RNA levels and aromatase protein through quantitative RT‐PCR and W estern blotting, respectively. Adenomyosis and adenocarcinomatous changes were significantly discernible in the EE 2 ‐exposed uteri, and incidence of ectopic glands and serous cysts were significantly increased in the prenatally EE 2 ‐exposed ovaries as compared with respective controls. Significant upregulation of the aromatase m RNA was seen in the prenatally EE 2 ‐exposed uteri and in the EE 2 ‐exposed ovaries. The aromatase protein was identified in all ovaries examined, and in EE 2 ‐exposed uteri but not in controls and confirmed its localization in eutopic and ectopic glands, abnormally proliferated lesions and the lining of the cysts. Taken together, continuous EE 2 exposure may cause endometriotic and precancerous lesions due to excessive estrogen synthesis in both target organs.