Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice

Takeshi Nakamura, Shinichi Miyagawa, Yoshinao Katsu, Hajime Watanabe, Takeshi Mizutani, Tomomi Sato, Ken Ichirou Morohashi, Takashi Takeuchi, Taisen Iguchi, Yasuhiko Ohta

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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 α 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.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalToxicology
Volume296
Issue number1-3
DOIs
Publication statusPublished - Jun 14 2012

All Science Journal Classification (ASJC) codes

  • Toxicology

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