Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta.

Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta.
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DOI:
10.1016/j.envint.2014.06.006
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发表时间:
2014-10
影响因子:
11.8
通讯作者:
Baccarelli, Andrea A.
Baccarelli, Andrea A.
中科院分区:
环境科学与生态学1区
文献类型:
--
作者:
Vilahur, Nadia;Bustamante, Mariona;Byun, Hyang-Min;Fernandez, Mariana F.;Santa Marina, Loreto;Basterrechea, Mike;Ballester, Ferran;Murcia, Mario;Tardon, Adonina;Fernandez-Somoano, Ana;Estivill, Xavier;Olea, Nicolas;Sunyer, Jordi;Baccarelli, Andrea A.

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产前暴露于内分泌干扰化合物(EDCs)以前已被证明会改变表观遗传标记。在这项工作中,我们探讨是否产前暴露于混合物的异种雌激素有可能改变胎盘表观基因组,通过研究DNA甲基化的逆转录转座子作为全球DNA甲基化的替代。生物标志物总有效异雌激素负荷(TEXB)在纵向INMA项目参与者的192个胎盘中进行了测量。采用亚硫酸氢盐焦磷酸测序法对10种不同的逆转录转座子(包括3种不同的长散布核元件(LINEs)、4种短散布核元件(西内斯)和3种人内源性逆转录病毒(HERVs))的DNA甲基化进行定量评估。协会进行了测试,使用线性混合效应回归模型和性别相互作用进行了评估。对于Yb 8,观察到显著的性别相互作用(相互作用的p值<0.001,在Bonferroni校正的p值阈值0.0025处显著)。与第一个三分位数相比,具有最高TEXB-α暴露水平的男孩(第三个三分位数)的甲基化平均降低了0.84%(p值<0.001),而在女孩中没有发现显著影响(p值= 0.134)。我们的研究结果表明,男孩可能更容易受到影响,暴露于外源性雌激素在产前发展,生产的DNA甲基化的某些敏感的基因组重复序列在组织中的变化,对胎儿的生长和发育的重要性。
Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. The biomarker Total Effective Xenoestrogen Burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retrovirus (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. A significant sex interaction was observed for AluYb8 (p value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p value<0.001), while no significant effects were found in girls (p value= 0.134). Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.
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发表时间: 2010-07-05
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影响因子: --
作者:
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