title: Delayed adverse effects of neonatal exposure to diethylstilbestrol and their dose dependency in female rats.
abstract: Neonatal exposure to estrogenic chemicals causes irreversible complex damage to the hypothalamus-pituitary-gonadal 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 µg/kg bw after birth. All except the lowest dose had estrogenic activity in a uterotrophic assay. All rats at 1500 µg/kg and some at 150 µg/kg showed abnormal morphologies in the genital tract, indicating they were androgenized before maturation. Although no morphological abnormalities were noted at 15 µg/kg or lower, onset of persistent estrus was significantly accelerated in the 1.5, 15, and 150 µg/kg groups with dose dependency, and the latest onset was from seventeen to twenty-one weeks of age at 1.5 µg/kg. The neonatal exposure to DES increased uterine adenocarcinoma development only at 150 µg/kg, although uterine anomalies were detected at 1,500 µg/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.
authors: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan. midoriy@nihs.go.jp
authors: Midori
authors: M
authors: Yoshida
authors: Miwa
authors: M
authors: Takahashi
authors: Kaoru
authors: K
authors: Inoue
authors: Seigo
authors: S
authors: Hayashi
authors: Akihiko
authors: A
authors: Maekawa
authors: Akiyoshi
authors: A
authors: Nishikawa
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D004054:Diethylstilbestrol / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle; D005260:Female; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014594:Uterine Neoplasms / Q000139:chemically induced* / Q000473:pathology; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014621:Vagina / Q000187:drug effects / Q000473:pathology
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004054:Diethylstilbestrol