Effect of prenatal exposure to phthalates on epigenome-wide DNA methylations in cord blood and implications for fetal growth: The Hokkaido Study on Environment and Children's Health
Effect of prenatal exposure to phthalates on epigenome-wide DNA methylations in cord blood and implications for fetal growth: The Hokkaido Study on Environment and Children's Health
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DOI：
10.1016/j.scitotenv.2021.147035
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发表时间：
2021-04-17
影响因子：
9.8
通讯作者：
Kishi, Reiko
中科院分区：
文献类型：
--
作者：
Miura, Ryu;Ikeda-Araki, Atsuko;Kishi, Reiko
出生前接触邻苯二甲酸盐会对后代的健康产生负面影响。特别是，表观遗传改变，如DNA甲基化，可能会将邻苯二甲酸盐暴露与健康结果联系起来。在这里，我们评估了宫内邻苯二甲酸二乙基己酯(DEHP)暴露与脐带血表观基因组DNA甲基化的关系，研究对象为203对登记在北海道环境与儿童健康研究中的母子，使用Illumina HumanMethylation450 BeadChip。表观基因组关联分析表明，母血中DEHP的主要代谢物邻苯二甲酸单(2-乙基己基)酯(MEHP)水平与脐血DNA甲基化水平之间存在显著的正相关。与MEHP水平呈正相关的CPGS基因丰富了与代谢、内分泌系统和信号转导相关的通路。其中，参与代谢的CPGS甲基化水平与后代的体重指数(PI)呈负相关。此外，聚类和中介分析表明，多个甲基化增加的变化可能共同调节子宫内DEHP暴露与后代出生时PI的关联。虽然还需要进一步的研究来评估这些变化的影响，但这项研究表明，不同的DNA甲基化可能会将邻苯二甲酸盐在子宫中的暴露与胎儿生长联系起来，并进一步暗示DNA甲基化对后代肥胖具有预测价值。(C)2021年爱思唯尔公司保留所有权利。
Prenatal exposure to phthalates negatively affects the offspring's health. In particular, epigenetic alterations, such as DNA methylation, may connect phthalate exposure with health outcomes. Here, we evaluated the association of di-2-ethylhexyl phthalate (DEHP) exposure in utero with cord blood epigenome-wide DNA methylation in 203 mother-child pairs enrolled in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analysis demonstrated the predominant positive associations between the levels of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), in maternal blood and DNA methylation levels in cord blood. The genes annotated to the CpGs positively associated with MEHP levels were enriched for pathways related to metabolism, the endocrine system, and signal transduc-tion. Among them, methylation levels of CpGs involved in metabolism were inversely associated with the offspring's ponderal index (PI). Further, clustering and mediation analyses suggested that multiple increased methylation changes may jointly mediate the association of DEHP exposure in utero with the offspring's PI at birth. Although further studies are required to assess the impact of these changes, this study suggests that differential DNA methylation may link phthalate exposure in utero to fetal growth and further imply that DNA methylation has predictive value for the offspring's obesity.(c) 2021 Elsevier B.V. All rights reserved.