In utero exposure to low doses of Bisphenol A lead to long-term deleterious effects in the vagina
In utero exposure to low doses of Bisphenol A lead to long-term deleterious effects in the vagina
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DOI：
10.1038/sj.neo.7900212
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发表时间：
2002-03-01
期刊：
影响因子：
4.8
通讯作者：
Chahoud, L
中科院分区：
文献类型：
--
作者：
Schönfelder, G;Flick, B;Chahoud, L
“内分泌干扰物假说”的起源可以追溯到有关青春期女儿的报道，这些女儿的母亲在怀孕期间服用了高效合成雌激素己烯雌酚，并患上了一种罕见的阴道癌和腺癌。双酚A(BPA)是一种雌激素化学物质，广泛用于制造各种消费品。一些观察性研究表明，我们暴露在BPA中的量可能会改变发育中的啮齿动物的生殖器官。我们研究了低剂量双酚A的影响，以解决以下问题：(A)宫内暴露是否会影响后代的阴道，以及(B)是什么机制导致了毒性影响。孕鼠每天给予0.1 mg/kg(低剂量)或50 mg/kg BPA(未观察到的效应水平)或0.2 mg/kg/d的17α-乙炔雌二醇灌胃。在青春期后后代的阴道中观察到显著的形态变化，这导致我们检测阴道雌激素受体(ER)的表达，因为BPA与ERα结合，这对阴道上皮的生长至关重要。我们发现，与对照组相比，暴露于任一剂量双酚A的雌性子代在发情期不表达全长Era，而在发情间期，Era的表达与对照组没有差异。ERa下调似乎是观察到的阴道形态改变的原因。
The origins of the "endocrine disrupter hypothesis" may be traced to reports on adolescent daughters born to women who had taken the highly potent synthetic estrogen, diethylstilbestrol, while pregnant, and who developed a rare form of vaginal cancer and adenocarcinoma. Bisphenol A (BPA) is an estrogenic chemical that Is highly employed in the manufacture of a wide range of consumer products. Some observational studies have suggested that the amounts of BPA to which we are exposed could alter the reproductive organs of developing rodents. We examined the influence of BPA at low doses to address the questions of (a) whether in utero exposure affects the vagina of the offspring and (b) which mechanisms cause the toxic effects. Gravid Sprague-Dawley dams were administered either 0.1 (low dose) or 50 mg/kg per day BPA, the no observed effect level, or 0.2 mg/kg per day 17alpha-ethinyl estradiol by gavage. Striking morphological changes were observed in the vagina of postpubertal offspring leading us to examine vaginal estrogen receptor (ER) expression because BPA binds to the ERalpha, which is important for growth of the vaginal epithelium. We show that the full-length ERa is not expressed during estrus in the vagina of female offspring exposed to either dose of BPA when compared to the control group, whereas ERa expression does not differ from the control group during the diestrus stage. ERalpha downregulation seems to be responsible for the observed altered vaginal morphology.