title: 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.affiliation: Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan. mtakahashi@nihs.go.jp
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Tomomi
authors.initials: T
authors.lastname: Morikawa
authors.forename: Saori
authors.initials: S
authors.lastname: Matsuo
authors.forename: Seigo
authors.initials: S
authors.lastname: Hayashi
authors.forename: Kei
authors.initials: K
authors.lastname: Tamura
authors.forename: Gen
authors.initials: G
authors.lastname: Watanabe
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Taya
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D000858:Anovulation / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D002273:Carcinogens; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D006965:Hyperplasia / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014594:Uterine Neoplasms / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D014599:Uterus / Q000187:drug effects* / Q000473:pathology; D014621:Vagina / Q000187:drug effects / Q000254:growth & development
chemical_list: D002273:Carcinogens; D004967:Estrogens; D008769:Methylnitronitrosoguanidine; D004997:Ethinyl Estradiol; C013525:ENNG; D011374:Progesterone; D004958:Estradiol
keywords: 17Alpha-ethynylestradiol; 17α-ethynylestradiol; DES; Delayed effects; E2; EE; ENNG; Estrous cycle; FSH; HPG; LH; N-ethyl-N′-nitro-N-nitrosoguanidine; Neonatal exposure; P4; PND; PRL; Uterine carcinogenesis; diethylstilbestrol; estradiol-17β; follicle-stimulating hormone; hypothalamus-pituitary-gonadal; lutenizing hormone; postnatal day; progesterone; prolactin