MSX2 promotes vaginal epithelial differentiation and wolffian duct regression and dampens the vaginal response to diethylstilbestrol

Molecular Endocrinology
Yan YinLiang Ma

Abstract

In utero exposure to diethylstilbestrol (DES) leads to patterning defects in the female reproductive tract (FRT) and a propensity to the development of vaginal adenocarcinomas in humans. In the mouse, DES treatment similarly induces a plethora of FRT developmental defects, including stratification of uterine epithelium and presence of glandular tissue in cervix and vagina. Uterine abnormalities are associated with repression of the homeobox gene Msx2, and DES leads to an altered uterine response in Msx2 mutants including a dilated uterine lumen. Here we investigate the role of Msx2 in normal vaginal development and in FRT response to DES. During vaginal development, Msx2 is required for Tgfbeta2 and Tgfbeta3 expression and for proper vaginal epithelial differentiation. Moreover, Msx2 is involved in caudal Wolffian duct regression by promoting apoptosis. Consistently, neonatal DES exposure represses Msx2 expression in the Wolffian duct epithelium and inhibits its apoptosis and subsequent regression. Intriguingly, although DES treatment also represses Msx2 expression in the vaginal epithelium, a much more severe DES-induced vaginal phenotype was observed in Msx2 mutant mice, including a complete failure of Müllerian vaginal epith...Continue Reading

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Citations

Sep 29, 2007·Molecular Endocrinology·Yan YinLiang Ma
Mar 3, 2011·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Katherine Stewart, Maxime Bouchard
Feb 22, 2012·Molecular Aspects of Medicine·Dan ZhangHe-Feng Huang
Jul 9, 2010·Frontiers in Neuroendocrinology·Aparna Mahakali Zama, Mehmet Uzumcu
Aug 28, 2009·Trends in Endocrinology and Metabolism : TEM·Liang Ma
Apr 17, 2009·Genesis : the Journal of Genetics and Development·Congxing LinLiang Ma
May 24, 2011·Developmental Biology·Congxing LinLiang Ma
Aug 5, 2020·Reproductive Sciences·Renu BalaKiran Singh
Sep 9, 2021·Biology of Reproduction·Andrew T MajorCraig A Smith

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