Involvement of growth factors in induction of persistent proliferation of vaginal epithelium of mice exposed neonatally to diethylstilbestrol.
Neonatal treatment of female mice with natural and synthetic estrogens including diethylstilbestrol (DES) results in persistent proliferation and cornification of vaginal epithelium. In order to study the mechanism of persistent proliferation of vaginal epithelium, histological and biochemical changes were examined in the vagina of C57BL female mice exposed neonatally to 3 microg DES for 5 days. In intact control adult mice, ovariectomy induced apoptotic cell death in vaginal epithelial cells detected by in situ 3'-DNA nick end labeling method accompanied by low DNA synthesis detected by incorporation of bromodeoxyuridine. In neonatally DES-exposed adult mice, however, ovariectomy did not induce reduction of DNA synthesis and showed only a slight increase in apoptotic cells of vaginal epithelium. In neonatally DES-exposed mouse vagina, semi-quantitative reverse transcription polymerase chain reaction revealed a continuous higher expression of mRNAs encoding epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). These results indicate that neonatal DES exposure causes the increase in expression of EGF and TGF-alpha mRNA, possibly resulting in the induction of persistent proliferation and cornification of vaginal epithelium in mice.
Sato
Tomomi
T
Graduate School of Integrated Science, Yokohama City University, Yokohama 236-0027, Japan.
Fukazawa
Yugo
Y
Ohta
Yasuhiko
Y
Iguchi
Taisen
T
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000633:toxicity*; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D002273:Carcinogens; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D004054:Diethylstilbestrol; D004247:DNA; D001973:Bromodeoxyuridine