{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:26:29Z","timestamp":1791023189686,"version":"4.1.0"},"reference-count":48,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2011,7,11]],"date-time":"2011-07-11T00:00:00Z","timestamp":1310342400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>Neonatal exposure to estrogenic chemicals causes irreversible complex damage to the hypothalamus\u2013pituitary\u2013gonadal axis and reproductive system in females. Some lesions are noted after maturation as delayed adverse effects. We investigated the characteristics and dose dependence of delayed effects using female rats neonatally exposed to diethylstilbestrol (DES). Female Donryu rats were subcutaneously injected with a single dose of DES of 0 (control), 0.15, 1.5, 15, 150, or 1,500 \u00b5g\/kg bw after birth. All except the lowest dose had estrogenic activity in a uterotrophic assay. All rats at 1500 \u00b5g\/kg and some at 150 \u00b5g\/kg showed abnormal morphologies in the genital tract, indicating they were androgenized before maturation. Although no morphological abnormalities were noted at 15 \u00b5g\/kg or lower, onset of persistent estrus was significantly accelerated in the 1.5, 15, and 150 \u00b5g\/kg groups with dose dependency, and the latest onset was from seventeen to twenty-one weeks of age at 1.5 \u00b5g\/kg. The neonatal exposure to DES increased uterine adenocarcinoma development only at 150 \u00b5g\/kg, although uterine anomalies were detected at 1,500 \u00b5g\/kg. These results indicate that neonatal exposure to DES, which exerts estrogenic activity in vivo, induces delayed adverse effects in female rats in a dose-dependent manner. Early onset of persistent estrus appears to be the most sensitive parameter.<\/jats:p>","DOI":"10.1177\/0192623311413785","type":"journal-article","created":{"date-parts":[[2011,7,12]],"date-time":"2011-07-12T02:29:23Z","timestamp":1310437763000},"page":"823-834","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Delayed Adverse Effects of Neonatal Exposure to Diethylstilbestrol and Their Dose Dependency in Female Rats"],"prefix":"10.1177","volume":"39","author":[{"given":"Midori","family":"Yoshida","sequence":"first","affiliation":[{"name":"Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwa","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Inoue","sequence":"additional","affiliation":[{"name":"Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Chemical Management Center, National Institute of Technology and Evaluation, 2-24-10, Nishihara, Shibuya-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyoshi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,7,11]]},"reference":[{"key":"bibr1-0192623311413785","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.18146"},{"key":"bibr2-0192623311413785","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.078261"},{"key":"bibr3-0192623311413785","first-page":"789","volume":"85","author":"Ando-Lu J.","year":"1994","journal-title":"J Cancer Sci"},{"key":"bibr4-0192623311413785","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod62.1.95"},{"key":"bibr5-0192623311413785","doi-asserted-by":"publisher","DOI":"10.1042\/bj1640423"},{"key":"bibr6-0192623311413785","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2008.06.008"},{"key":"bibr7-0192623311413785","first-page":"4165","volume":"47","author":"Bern H. 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