Effect of neonatal exposure to DES in Fas and Bcl-2 expression in the adult mouse vagina and approach to the DES syndrome.
Neonatal exposure to a synthetic estrogen, diethylstilbestrol (DES), induces the ovary-independent persistent proliferation of vaginal epithelium in mice. Mouse vagina at the estrous stage in the normal estrous cycle shows 10 to 15 layers of epithelium with superficial keratinized layers, and ovariectomy induces a decrease of these epithelial cell layers and lymphocyte infiltration. Thus, cell proliferation and regression of vaginal epithelium are ovary dependent. Neonatally DES-treated mouse vagina showed the same phenotype as normal mouse vagina at the estrous stage, but ovariectomy did not induce a decrease of epithelial cell layers or a lymphocyte infiltration, and there was persistent proliferation of vaginal epithelium even after ovariectomy. In addition, apoptotic cell death characterized by oligonucleosomal DNA fragmentation, Fas expression, and Bcl-2 downregulation were induced after ovariectomy in normal mouse vagina, but not in DES-treated mouse vagina. These results suggest that neonatal DES-exposure in mice prevents vaginal Fas-mediated apoptosis following the downregulation of Bcl-2, and these abnormalities in expression are involved in persistent proliferation of the vaginal epithelium.
Suzuki
A
A
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Enari
M
M
Iguchi
T
T
D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens / Q000633:toxicity*; D004054:Diethylstilbestrol / Q000633:toxicity*; D004848:Epithelium / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014621:Vagina / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D019014:fas Receptor / Q000032:analysis / Q000235:genetics*
D002273:Carcinogens; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019014:fas Receptor; D004054:Diethylstilbestrol