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首页 » 生物研究 » FASEB J:胎儿双酚A暴露或引发其青春期后患雌激素相关的疾病

FASEB J:胎儿双酚A暴露或引发其青春期后患雌激素相关的疾病

来源:生物谷 2016-06-21 09:38

2016年6月21日讯/生物谷BIOON/--接触低水平的BPA(双酚A)或许是安全的,但近日刊登在The FASEB Journal杂志上的一项研究报告中,来自耶鲁大学的研究人员发现,在胎儿发育期间,暴露于BPA中或许可以永久性地改变小鼠子宫的基因组,而这些改变或可影响小鼠机体中受雌激素调节的基因的表达,同时这些改变也会引发雌激素相关疾病的发生,比如不孕、子宫内膜异位症、子宫内膜癌、骨质疏松症、前列腺癌、神经变性疾病、肥胖及乳腺癌的发生。

研究者Hugh S. Taylor认为,我们的研究表明,胎儿接触BPA或可引发成年后子宫对雌激素差生反应的过程中发生一种有害性的改变,本文研究证实,BPA是一种活性化合物,其可以负向影响胎儿的发育,而且女性在怀孕期间应当尽量减少母源性BPA的摄入或暴露接触。

文章中,研究者Taylor及其同事利用两组怀孕小鼠进行研究,其中一种接受腹腔内灌注人类暴露范围内的BPA,另外一组则不进行灌注;随后研究人员在雌性小鼠性成熟之前分析其子宫的遗传和表观遗传学特性,同时对每一组小鼠进行研究,检测了子宫基因对雌激素的反应,他们发现,尽管小鼠子宫的改变并不是在出生时或出生后的一段时间内产生的,但性成熟后这些改变会变得非常明显,本文研究中我们就揭示了胎儿在接触BPA后几乎1000个基因对雌激素反应所产生的改变。

最后杂志主编Thoru Pederson表示,这项研究揭示了BPA暴露对胎儿的影响,同时也阐述了BPA对小鼠后代机体子宫基因表达效应的影响,当然随着研究深入,该研究结果或可转化到人类机体的研究中,而研究者也非常希望有一天可以进行人类机体的相关研究。(生物谷Bioon.com)

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Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure

Elisa M. Jorgensen1, Myles H. Alderman III1 and Hugh S. Taylor2

Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure to BPA in utero has been linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine epigenome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine epigenome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-α (ERα)–binding genes. The majority of genes that demonstrated both altered expression and ERα binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the epigenome of genes that bind ERα. Gene–environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen-related disease in adults.—Jorgensen, E. M., Alderman, M. H., III, Taylor, H. S. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure.

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