School of Public Health, Seoul National University, Seoul 08826, Republic of Korea.
Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Environ Int. 2018 Oct;119:398-406. doi: 10.1016/j.envint.2018.06.039. Epub 2018 Jul 10.
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.
产前暴露于持久性有机污染物（POPs）已在许多流行病学研究中与新生儿的许多不良出生结局相关。尽管表观遗传修饰被认为是这些关联的可能解释之一，但研究很少报道怀孕期间 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 POP（包括有机氯农药（OCPs）、多溴联苯醚（PBDEs）和多氯联苯（PCBs））与长散布元件 1（LINE-1）以及胎盘 DNA 中印迹基因甲基化水平之间的关联，在韩国母婴对中（N=109）。我们评估了 DNA 甲基化与每个目标 POP（单-POP 模型）的关联，以及应用主成分分析（多-POP 模型）的多种 POP 之间的关联。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 甲基化之间存在显著关联。分娩期间采集的母体血清中β-六氯环己烷（β-HCH）浓度升高与胎盘内 LINE-1 甲基化降低显著相关。母体血清中 p,p'-二氯二苯三氯乙烷（p,p'-DDT）水平较高与胰岛素样生长因子 2（IGF2）的超甲基化相关。在多-POP 模型中，还观察到 DDTs 与 IGF2 甲基化之间存在显著正相关。胎盘 LINE-1 甲基化与出生长度呈负相关。我们的观察结果表明，产前暴露于包括 DDT 在内的几种 POP 与基因甲基化的变化有关，包括胎盘内主要印迹基因。在发育过程中，这些胎盘表观遗传改变的后果值得进一步研究。
