Developmental effects of ethinylestradiol on reproductive organs of female mice.
Reproductive organs in female mice are susceptible to exposure to estrogenic substances especially during development. In the present study, C57BL/6J female mice were exposed to the synthetic estrogens ethinylestradiol (EE2) or diethylstilbestrol (DES), 10-100 or 6.7-67 microg/kg bw, respectively, in utero from day 10 to 18 of pregnancy, and their effects were analyzed at 30 and 40 days of age. Both EE2 and DES reduced the survival rate of fetuses and newborns in a dose-dependent manner. Polyovular follicles (PF) were found in the ovaries of all groups at 30 days of age including oil-injected controls. However, the incidence of PF was significantly higher in the 50 microg/kg EE2- and 33.3 microg/kg DES-exposed mice than the control. In vaginal epithelia of the in utero EE2 exposed, ovariectomized mice, stratification and cornification were encountered even 10 days after ovariectomy. Especially, vaginae in the ovariectomized mice given high dose of EE2 or DES in utero showed ovary-independent proliferation of the epithelium. Thus, it is clear that prenatal exposure to EE2 or DES induces reproductive abnormalities, including PF, ovary-independent vaginal epithelial stratification and cornification.
Kirigaya
Akiko
A
Graduate School of Integrated Science, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan.
Hayashi
Shinji
S
Iguchi
Taisen
T
Sato
Tomomi
T
D000014:Abnormalities, Drug-Induced / Q000401:mortality / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D004967:Estrogens / Q000494:pharmacology / Q000633:toxicity; D004997:Ethinyl Estradiol / Q000494:pharmacology* / Q000633:toxicity; D005187:Fallopian Tubes / Q000187:drug effects / Q000473:pathology; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005836:Genitalia, Female / Q000187:drug effects / Q000473:pathology*; D008098:Litter Size / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D015996:Survival Rate; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014621:Vagina / Q000187:drug effects / Q000473:pathology
D004967:Estrogens; D004997:Ethinyl Estradiol; D004054:Diethylstilbestrol