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Prenatal exposure to persistent organic pollutants and methylation of LINE-1 and imprinted genes in placenta: A CHECK cohort study
Environment International ( IF 11.8 ) Pub Date : 2018-07-10 , DOI: 10.1016/j.envint.2018.06.039
Sujin Kim , Yoon Hee Cho , Inae Lee , Wonji Kim , Sungho Won , Ja-Lok Ku , Hyo-Bang Moon , Jeongim Park , Sungkyoon Kim , Gyuyeon Choi , Kyungho Choi

Prenatal exposure to persistent organic pollutants (POPs) has been linked to numerous adverse birth outcomes among newborn infants in many epidemiological studies. Although epigenetic modifications have been suggested as possible explanations for those associations, studies have rarely reported a relationship between POP exposure during pregnancy and DNA methylation in the placenta.

In the present study, we investigated the association between prenatal exposure to several POPs, including organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs), and methylation levels of long interspersed element 1 (LINE-1), as well as imprinted genes in placental DNAs among Korean mother-child pairs (N = 109). We assessed the association of DNA methylation not only with each target POP (single-POP models) but also with multiple POPs applying principal component analysis (multiple-POP models). Potential associations between placental DNA methylation and birth outcomes of newborn infants were also estimated.

In single-POP models, significant associations were detected between OCP measurements and placental DNA methylation. Elevated concentrations of β-hexachlorhexane (β-HCH) in maternal serum collected during delivery were significantly associated with a decrease in methylation of LINE-1 in the placenta. Higher levels of p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT) in maternal serum were associated with hypermethylation of insulin-like growth factor 2 (IGF2). In multiple-POP models, a significant and positive association between DDTs and IGF2 methylation was also observed. Placental LINE-1 methylation was inversely associated with birth length. Our observations indicate that prenatal exposure to several POPs including DDTs is associated with the changes in methylation of genes, including major imprinted genes in the placenta. The consequences of these epigenetic alterations in placenta during development deserve further investigation.



中文翻译:

产前暴露于持久性有机污染物以及胎盘中LINE-1和印迹基因甲基化的一项CHECK队列研究

在许多流行病学研究中,产前暴露于持久性有机污染物(POPs)与新生婴儿的许多不良出生结局有关。尽管已提出表观遗传修饰可能是这些关联的解释,但研究很少报道妊娠期间POP暴露与胎盘DNA甲基化之间的关系

在本研究中,我们调查了产前暴露于几种持久性有机污染物(包括有机氯农药(OCP),多溴联苯醚(PBDEs)和多氯联苯(PCB))与长时间散布的元素1(LINE-1)的甲基化水平之间的关系。以及韩国母子对之间胎盘DNA中的印迹基因(N = 109)。我们不仅评估了DNA甲基化与每个目标POP的关联(单个POP模型),还评估了应用主成分分析的多个POP的关联(多个POP模型)。还估计了胎盘DNA甲基化与新生儿出生结局之间的潜在关联。

在单POP模型中,检测到OCP测量值与胎盘DNA甲基化之间存在显着关联。分娩过程中收集的母体血清中β-六氯己烷(β-HCH)浓度升高与胎盘中LINE-1甲基化的降低显着相关。孕妇血清中较高的pp'-二氯二苯基三氯乙烷(pp' -DDT)水平与胰岛素样生长因子2IGF2)的高甲基化有关。在多种POP模型中,滴滴涕与IGF2之间存在显着的正相关关系还观察到甲基化。胎盘LINE-1甲基化与出生时长成反比。我们的观察结果表明,产前暴露于包括DDTs在内的几种POP与基因甲基化的变化有关,包括胎盘中的主要印迹基因。这些在发育过程中胎盘的表观遗传学改变的后果值得进一步研究。

更新日期:2018-07-12
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