Hokkaido University Center for Environmental and Health Sciences, Sapporo, Japan.
Department of Health Sciences, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan.
Sci Rep. 2019 Aug 26;9(1):12369. doi: 10.1038/s41598-019-48916-5.
Exposure to bisphenol A (BPA) in utero is associated with adverse health outcome of the offspring. Differential DNA methylation at specific CpG sites may link BPA exposure to health impacts. We examined the association of prenatal BPA exposure with genome-wide DNA methylation changes in cord blood in 277 mother-child pairs in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation 450 BeadChip. We observed that a large portion of BPA-associated differentially methylated CpGs with p-value < 0.0001 was hypomethylated among all newborns (91%) and female infants (98%), as opposed to being hypermethylated (88%) among males. We found 27 and 16 CpGs with a false discovery rate (FDR) < 0.05 in the analyses for males and females, respectively. Genes annotated to FDR-corrected CpGs clustered into an interconnected genetic network among males, while they rarely exhibited any interactions in females. In contrast, none of the enrichment for gene ontology (GO) terms with FDR < 0.05 was observed for genes annotated to the male-specific CpGs with p < 0.0001, whereas the female-specific genes were significantly enriched for GO terms related to cell adhesion. Our epigenome-wide analysis of cord blood DNA methylation implies potential sex-specific epigenome responses to BPA exposure.
子宫内暴露于双酚 A（BPA）与后代的健康结果不良有关。特定 CpG 位点的差异 DNA 甲基化可能将 BPA 暴露与健康影响联系起来。我们使用 Illumina HumanMethylation 450 BeadChip，在北海道环境与儿童健康研究中对 277 对母婴进行了研究，检查了产前 BPA 暴露与脐带血全基因组 DNA 甲基化变化的关联。我们观察到，在所有新生儿（91%）和女婴（98%）中，与 BPA 相关的差异甲基化 CpG 中很大一部分（p 值<0.0001）呈低甲基化状态，而在男婴中（88%）则呈高甲基化状态。我们分别在男性和女性的分析中发现了 27 个和 16 个 FDR<0.05 的 CpG。注释到 FDR 校正 CpG 的基因在男性中聚类成一个相互连接的遗传网络，而在女性中很少表现出任何相互作用。相比之下，在注释到男性特异性 CpG（p<0.0001）的基因中，没有观察到任何与 FDR<0.05 的基因本体论 (GO) 术语富集，而女性特异性基因则显著富集了与细胞黏附相关的 GO 术语。我们对脐带血 DNA 甲基化的全基因组表观基因组分析表明，BPA 暴露可能存在潜在的性别特异性表观基因组反应。
