■接触环境化学物质,如邻苯二甲酸酯,酚类物质,和多环芳烃(PAHs)在怀孕期间会增加不良新生儿结局的风险。我们探讨了母体暴露于环境化学物质与脐带血单核细胞(CBMC)和胎盘组织(母体和胎儿侧)中DNA甲基化之间的关联,以确定这些关联的潜在机制。
这项研究包括75名计划在2014年至2017年间在辛辛那提大学医院分娩的孕妇。在分娩访视期间收集母体尿液样本,并分析37种酚类生物标志物(12),邻苯二甲酸酯(13),邻苯二甲酸酯替代品(4),和PAHs(8)。还收集脐带血和胎盘组织(母体和胎儿侧)以使用InfiniumHumanMethomethylation450KBeadChip测量DNA甲基化强度。我们使用线性回归,调整潜在的混杂因素,评估与妊娠化学暴露相关的CBMC(n=54)和胎盘[胎儿(n=67)和母体(n=68)侧]的CpG特异性甲基化变化(本研究中测量的37项生物标志物中的29项).要考虑多个测试,我们使用错误发现率q值<0.05,并通过用1±0.5的基因组膨胀因子限制结果来呈现结果.此外,使用京都基因百科全书和基因组学途径进行基因集富集分析。
■在评估差异甲基化的29种化学生物标志物中,PAH代谢物的母体浓度(1-羟基萘,2-羟基芴,4-羟基菲,1-羟基芘),邻苯二甲酸单羧基异壬酯,邻苯二甲酸单-3-羧基丙基酯,和双酚A与胎盘(母体或胎儿侧)的甲基化改变有关。在与表观遗传变化相关的暴露生物标志物中,1-羟基萘,和邻苯二甲酸单-3-羧基丙酯与胎盘中差异CpG甲基化一致相关。基因富集分析表明,母体1-羟基萘与胎盘的脂质代谢和细胞过程有关。此外,邻苯二甲酸单-3-羧基丙酯与胎盘的有机系统和遗传信息处理有关。
■在分娩期间评估的29种化学生物标志物中,1-羟基萘和邻苯二甲酸单-3-羧基丙酯与胎盘中的DNA甲基化有关。
■在线版本包含10.1186/s43682-024-00027-7提供的补充材料。
UNASSIGNED: Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations.
UNASSIGNED: This study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and
placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC (n = 54) and
placenta [fetal (n = 67) and maternal (n = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways.
UNASSIGNED: Among the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the
placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the
placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta.
UNASSIGNED: Among the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the
placenta.
UNASSIGNED: The online version contains supplementary material available at 10.1186/s43682-024-00027-7.