Epigenetic marks are key biomarkers linking the prenatal environment to health and development. However, DNA methylation associations and persistence of marks for prenatal exposure to multiple Endocrine Disrupting Chemicals (EDCs) in human populations have not been examined in great detail. We measured Bisphenol-A (BPA), triclosan, benzophenone-3 (BP3), methyl-paraben, propyl-paraben, and butyl-paraben, as well as 11 phthalate metabolites, in two pregnancy urine samples, at approximately 13 and 26 weeks of gestation in participants of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (N = 309). DNA methylation of cord blood at birth and child peripheral blood at ages 9 and 14 years was measured with 450K and EPIC arrays. Robust linear regression was used to identify differentially methylated probes (DMPs), and was used to identify differentially methylated regions (DMRs) in association with pregnancy-averaged EDC concentrations. Quantile g-computation was used to assess associations of the whole phenol/phthalate mixture with DMPs and DMRs. Prenatal BPA exposure was associated with 1 CpG among males and Parabens were associated with 10 CpGs among females at Bonferroni-level significance in cord blood. Other suggestive DMPs (unadjusted p-value < 1 × 10) and several DMRs associated with the individual phenols and whole mixture were also identified. A total of 10 CpG sites at least suggestively associated with BPA, Triclosan, BP3, Parabens, and the whole mixture in cord blood were found to persist into adolescence in peripheral blood. We found sex-specific associations between prenatal phenol exposure and DNA methylation, particularly with BPA in males and Parabens in females. Additionally, we found several DMPs that maintained significant associations with prenatal EDC exposures at age 9 and age 14 years.

中文翻译：

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产前接触环境酚和邻苯二甲酸盐以及儿童时期 DNA 甲基化模式的改变


表观遗传标记是将产前环境与健康和发育联系起来的关键生物标记。然而，DNA 甲基化关联和人类产前接触多种内分泌干扰化学物质 (EDC) 的标记持续性尚未得到详细研究。我们在大约 13 周和 26 周的两份妊娠尿液样本中测量了双酚 A (BPA)、三氯生、二苯甲酮 3 (BP3)、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯和对羟基苯甲酸丁酯以及 11 种邻苯二甲酸酯代谢物。萨利纳斯母婴健康评估中心 (CHAMACOS) 研究参与者的妊娠期 (N = 309)。使用 450K 和 EPIC 阵列测量出生时脐带血以及 9 岁和 14 岁时儿童外周血的 DNA 甲基化。稳健线性回归用于识别差异甲基化探针 (DMP)，并用于识别与妊娠平均 EDC 浓度相关的差异甲基化区域 (DMR)。分位数 g 计算用于评估整个苯酚/邻苯二甲酸酯混合物与 DMP 和 DMR 的关联。产前 BPA 暴露与男性中的 1 个 CpG 相关，对羟基苯甲酸酯与女性中的 10 个 CpG 相关，在脐带血中具有 Bonferroni 水平显着性。还确定了其他暗示性 DMP（未调整的 p 值 < 1 × 10）和与单个酚和整个混合物相关的几个 DMR。总共 10 个 CpG 位点至少暗示与脐带血中的 BPA、三氯生、BP3、对羟基苯甲酸酯和整个混合物相关，被发现在外周血中持续到青春期。我们发现产前苯酚暴露与 DNA 甲基化之间存在性别特异性关联，尤其是男性的 BPA 和女性的对羟基苯甲酸酯。 此外，我们发现几种 DMP 与 9 岁和 14 岁时的产前 EDC 暴露保持显着关联。