Journal
TOXICOLOGY
Volume 296, Issue 1-3, Pages 13-19Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2012.02.010
Keywords
Adverse effects; Diethylstilbestrol; Mouse; Neonatal treatment; Wnt family genes
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Funding
- Ministry of Education, Culture, Sport, Science and Technology (B)
- Ministry of Health Labor and Welfare, Japan
- Grants-in-Aid for Scientific Research [24570074, 24510082, 22132002, 23570067] Funding Source: KAKEN
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Proliferation and differentiation of cells in female reproductive organs, the oviduct, uterus and vagina, are regulated by endogenous estrogen. In utero exposure to a synthetic estrogen, diethylstilbestrol (DES), induces vaginal clear-cell adenocarcinoma in humans. In mice, perinatal exposure to DES results in abnormalities such as polyovular follicles, uterine circular muscle disorganization and persistent vaginal epithelial cell proliferation. We reported the persistent gene expression change such as interleukin-1 (IL-1) related genes, insulin-like growth factor-I (IGF-I) and its downstream signaling in the mouse vagina exposed neonatally to DES. In this study, we found persistent up-regulation of Wnt4 and persistent down-regulation of Wnt11 in the vagina of mice exposed neonatally to DES and estrogen receptor a specific ligand. Also Wnt4 expression in vagina is correlated to the stratification of epithelial cells with the superficial keratinization of vagina, but not epithelial cell stratification only. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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