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.

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.

• Authors: Takeshi Nakamura, Shinichi Miyagawa, Yoshinao Katsu, Hajime Watanabe, Takeshi Mizutani, Tomomi Sato, Ken-Ichirou Morohashi, Takashi Takeuchi, Taisen Iguchi, Yasuhiko Ohta
• Journal: Toxicology (Toxicology) Vol. 296 Issue 1-3 Pg. 13-9 (Jun 14 2012) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 22445810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Estrogens, Non-Steroidal
• Interleukin-1
• RNA, Messenger
• Wnt Proteins
• Insulin-Like Growth Factor I
• Keratins
• Diethylstilbestrol

Topics

• Animals
• Animals, Newborn
• Cell Proliferation
• Diethylstilbestrol (toxicity)
• Epithelial Cells (drug effects, metabolism)
• Estrogens, Non-Steroidal (toxicity)
• Female
• Gene Expression Regulation (drug effects)
• Insulin-Like Growth Factor I (genetics)
• Interleukin-1 (genetics)
• Keratins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Oligonucleotide Array Sequence Analysis
• Ovary
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Vagina (cytology, drug effects, metabolism, pathology)
• Wnt Proteins (genetics)