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Estrogen receptor-alpha mediates the detrimental effects of neonatal diethylstilbestrol (DES) exposure in the murine reproductive tract.

Abstract：

:It is generally believed that estrogen receptor-dependent and -independent pathways are involved in mediating the developmental effects of the synthetic estrogen, diethylstilbestrol (DES). However, the precise role and extent to which each pathway contributes to the resulting pathologies remains unknown. We have employed the estrogen receptor knockout (ERKO) mice, which lack either estrogen receptor-alpha (alphaERKO or estrogen receptor-beta (betaERKO), to gain insight into the contribution of each ER-dependent pathway in mediating the effects of neonatal DES exposure in the female and male reproductive tract tissues of the mouse. Estrogen receptor-alpha female mice exhibited complete resistance to the chronic effects of neonatal DES exposure that were obvious in exposed wild-type animals, including atrophy and epithelial squamous metaplasia in the uterus; proliferative lesions of the oviduct; and persistent cornification of the vaginal epithelium. DES-mediated reduction in uterine Hoxa10, Hoxa11 and Wnt7a expression that occurs wild-type females during the time of exposure was also absent in alphaERKO females. In the male, alphaERKO mice exhibited complete resistance to the chronic effects of neonatal DES exposure on the prostate, including decreased androgen receptor levels, epithelial hyperplasia, and increased basal cell proliferation. Although ERbeta is highly expressed in the prostate epithelium, DES-exposed betaERKO males exhibited all of the effects of neonatal DES exposure that were observed in similarly exposed wild-type males. Therefore, the lack of DES-effects on gene expression and tissue differentiation in the alphaERKO uterus and prostate provides unequivocal evidence of an obligatory role for ERalpha in mediating the detrimental actions of neonatal DES exposure in the murine reproductive tract.

journal_name

Toxicology

journal_title

Toxicology

authors

Couse JF,Korach KS

doi

10.1016/j.tox.2004.06.046

keywords:

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

55-63

issue

1-2

eissn

0300-483X

issn

1879-3185

pii

S0300-483X(04)00365-8

journal_volume

205

pub_type

杂志文章,评审

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