Abstract：
BACKGROUND: 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.
METHODS: 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 comb-p 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.
RESULTS: 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 × 10-6) 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.
CONCLUSIONS: 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.
METHODS: 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 comb-p 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.
RESULTS: 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 × 10-6) 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.
CONCLUSIONS: 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.
摘要：
背景：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志物。然而,尚未对人群中产前暴露于多种内分泌干扰化学物质（EDC）的DNA甲基化关联和标记的持久性进行详细研究。
方法：我们测量了双酚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，在两份怀孕尿液样本中，萨利纳斯母亲和儿童健康评估中心（CHAMACOS）研究的参与者在妊娠约13周和26周时（N=309）。用450K和EPIC阵列测量出生时脐带血和9岁和14岁儿童外周血的DNA甲基化。稳健的线性回归用于鉴定差异甲基化探针（DMPs），和comb-p用于鉴定与妊娠平均EDC浓度相关的差异甲基化区域（DMRs）。分位数g-计算用于评估整个苯酚/邻苯二甲酸酯混合物与DMPs和DMRs的关联。
结果：男性产前BPA暴露与1个CpG相关，对羟基苯甲酸酯与10个CpG相关，女性脐带血中Bonferroni水平显著。还鉴定了与单个酚和整个混合物相关的其他暗示性DMP（未调整的p值<1×10-6）和几种DMR。共有10个CpG位点至少与BPA相关，三氯生,BP3,对羟基苯甲酸酯,发现脐带血中的整个混合物在外周血中持续到青春期。
结论：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在9岁和14岁时与产前EDC暴露保持显著关联.
方法：我们测量了双酚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，在两份怀孕尿液样本中，萨利纳斯母亲和儿童健康评估中心（CHAMACOS）研究的参与者在妊娠约13周和26周时（N=309）。用450K和EPIC阵列测量出生时脐带血和9岁和14岁儿童外周血的DNA甲基化。稳健的线性回归用于鉴定差异甲基化探针（DMPs），和comb-p用于鉴定与妊娠平均EDC浓度相关的差异甲基化区域（DMRs）。分位数g-计算用于评估整个苯酚/邻苯二甲酸酯混合物与DMPs和DMRs的关联。
结果：男性产前BPA暴露与1个CpG相关，对羟基苯甲酸酯与10个CpG相关，女性脐带血中Bonferroni水平显著。还鉴定了与单个酚和整个混合物相关的其他暗示性DMP（未调整的p值<1×10-6）和几种DMR。共有10个CpG位点至少与BPA相关，三氯生,BP3,对羟基苯甲酸酯,发现脐带血中的整个混合物在外周血中持续到青春期。
结论：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在9岁和14岁时与产前EDC暴露保持显著关联.
