EFFECT OF NEONATAL EXPOSURE TO DES IN FAS AND BCL-2 EXPRESSION IN THEADULT-MOUSE VAGINA AND APPROACH TO THE DES SYNDROME

Neonatal exposure to a synthetic estrogen, diethylstilbestrol (DES), i nduces the ovary-independent persistent proliferation of vaginal epith elium in mice, Mouse vagina at the estrous stage in the normal estrous cycle shows 10 to 15 layers of epithelium with superficial keratinize d layers, and ovariectomy induces a decrease of these epithelial cell layers and lymphocyte infiltration, Thus, cell proliferation and regre ssion of vaginal epithelium are ovary dependent, Neonatally DES-treate d mouse vagina showed the same phenotype as normal mouse vagina at the estrous stage, but ovariectomy did not induce a decrease of epithelia l cell layers or a lymphocyte infiltration, and there was persistent p roliferation of vaginal epithelium even after ovariectomy, In addition , apoptotic cell death characterized by oligonucleosomal DNA fragmenta tion, Fas expression, and Bcl-2 downregulation were induced after ovar iectomy in normal mouse vagina, but not in DES-treated mouse vagina, T hese results suggest that neonatal DES-exposure in mice prevents vagin al Fas-mediated apoptosis following the downregulation of Bcl-2, and t hese abnormalities in expression are involved in persistent proliferat ion of the vaginal epithelium. (C) 1996 Elsevier Science Inc.