title: Early indicators of delayed adverse effects in female reproductive organs in rats receiving neonatal exposure to 17alpha-ethynylestradiol.
abstract: We previously reported that neonatal exposure to 17α-ethynylestradiol (EE) led to delayed adverse effects in which age-related anovulation after sexual maturation was accelerated. To identify early indicators of these adverse effects, female Wistar Hannover GALAS rats received a single EE injection (0, 0.02, 0.2, 2, 20, or 200 μg/kg) within 24 hr of birth. Histopathological changes in ovarian and uterine development were investigated from postnatal day (PND) 14 to 10 weeks of age. Immunohistochemical expression of estrogen receptor alpha (ERα) in the uterus, serum levels of sex-related hormones and gene expression in the hypothalamus were examined. Although neonatal exposure to EE did not affect body growth or ovarian development, serum FSH tended to decrease at doses ≥ 2 μg/kg, and Kiss1 mRNA level in the whole hypothalamus was significantly decreased in all EE-treated groups at PND14.The number of uterine glands at PND21 was suppressed at doses ≥ 20 μg/kg, and ERα expression in the uterine epithelium at estrus stage decreased in a dose-dependent manner at 10 weeks of age. These results demonstrated that the various identified changes that occurred before the appearance of delayed adverse effects could be candidate early indicators.
authors.affiliation: Division of Pathology, National Institute of Health Sciences.
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: D000818:Animals; D000831:Animals, Newborn; D000858:Anovulation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism; D059648:Kisspeptins / Q000378:metabolism; D010053:Ovary / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D004997:Ethinyl Estradiol; D005640:Follicle Stimulating Hormone