Abstract
Neonatal diethylstilbestrol (DES) exposure elicits a wide range of abnormalities in the female mouse genital tract. This animal model system is suitable for investigating the mechanism of DES syndrome in humans. Accumulated evidence has shown that critical periods in development are present for distinct and permanent alterations in the female genital tract of mice exposed to DES neonatally (DES-mice). These effects of DES and other estrogens are mainly mediated by estrogen receptor α (ERα) through multiple pathways. Induction of ERα by DES exposure in neonatal stromal and epithelial cells, and successive premature activation of estrogen-regulated genes are thought to be essential to induce the abnormalities. Induction of malformation, permanent changes in estrogen-regulated genes, such as protooncogenes and growth factors, and carcinogenesis are assumed to be interdependent. This review focuses the following topics to discuss the molecular basis of DES-induced abnormalities mainly based on the results by histochemical techniques in the uterus: spatiotemporal expression of ERa and coactivators, proteins relating morphogenesis, and estrogen-regulated protooncogenes and growth factors.
Keywords: Growth factors, Protooncogenes, Hox, Wnt, Angiogenesis, Estrogen receptors, Female reproductive tract, Diethylstilbestrol
Current Pharmaceutical Design
Title: Expression of Estrogen-Regulated Genes During Development in the Mouse Uterus Exposed to Diethylstilbestrol Neonatally
Volume: 12 Issue: 12
Author(s): Shuji Yamashita
Affiliation:
Keywords: Growth factors, Protooncogenes, Hox, Wnt, Angiogenesis, Estrogen receptors, Female reproductive tract, Diethylstilbestrol
Abstract: Neonatal diethylstilbestrol (DES) exposure elicits a wide range of abnormalities in the female mouse genital tract. This animal model system is suitable for investigating the mechanism of DES syndrome in humans. Accumulated evidence has shown that critical periods in development are present for distinct and permanent alterations in the female genital tract of mice exposed to DES neonatally (DES-mice). These effects of DES and other estrogens are mainly mediated by estrogen receptor α (ERα) through multiple pathways. Induction of ERα by DES exposure in neonatal stromal and epithelial cells, and successive premature activation of estrogen-regulated genes are thought to be essential to induce the abnormalities. Induction of malformation, permanent changes in estrogen-regulated genes, such as protooncogenes and growth factors, and carcinogenesis are assumed to be interdependent. This review focuses the following topics to discuss the molecular basis of DES-induced abnormalities mainly based on the results by histochemical techniques in the uterus: spatiotemporal expression of ERa and coactivators, proteins relating morphogenesis, and estrogen-regulated protooncogenes and growth factors.
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Cite this article as:
Yamashita Shuji, Expression of Estrogen-Regulated Genes During Development in the Mouse Uterus Exposed to Diethylstilbestrol Neonatally, Current Pharmaceutical Design 2006; 12 (12) . https://dx.doi.org/10.2174/138161206776389840
DOI https://dx.doi.org/10.2174/138161206776389840 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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