Center for Research in Environmental Epidemiology (CREAL), Barcelona, Catalonia, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; Genomics and Disease Group, Bioinformatics and Genomics Program, Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain.
Center for Research in Environmental Epidemiology (CREAL), Barcelona, Catalonia, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; Genomics and Disease Group, Bioinformatics and Genomics Program, Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain.
Environ Int. 2014 Oct;71:81-7. doi: 10.1016/j.envint.2014.06.006. Epub 2014 Jun 28.
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 retroviruses (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.
先前的研究表明，产前暴露于内分泌干扰化合物 (EDC) 会改变表观遗传标记。
在这项工作中，我们通过研究反转录转座子中的 DNA 甲基化作为全基因组 DNA 甲基化的替代物，探索产前暴露于混合外源性雌激素是否有可能改变胎盘表观基因组。
在纵向 INMA 项目的 192 名参与者的胎盘样本中测量了生物标志物总有效外源性雌激素负担 (TEXB)。通过亚硫酸氢盐焦磷酸测序对 10 种不同的反转录转座子进行了定量评估，包括 3 种不同的长散布核元件 (LINEs)、4 种短散布核元件 (SINEs) 和 3 种人类内源性逆转录病毒 (HERVs)。使用线性混合效应回归模型测试关联，并评估性别交互作用。
观察到 AluYb8 存在显著的性别交互作用 (交互作用的 p 值<0.001，在 Bonferroni 校正的 p 值阈值 0.0025 下显著)。暴露于最高 TEXB-α 水平 (第三 tertile) 的男孩平均与第一 tertile 相比，甲基化水平降低了 0.84% (p 值<0.001)，而女孩中未发现显著影响 (p 值=0.134)。
我们的研究结果表明，男孩在产前发育过程中可能更容易受到外源性雌激素暴露的影响，导致某些对胎儿生长和发育重要的组织中特定敏感基因组重复序列的 DNA 甲基化发生变化。
