Epigenome-wide association study of gestational exposure to organophosphate esters and replacement brominated flame retardants with newborn DNA methylation

IF 8 1区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Science of the Total Environment Pub Date : 2025-07-17 DOI:10.1016/j.scitotenv.2025.180079

Angelico Mendy , Zana Percy , Joseph M. Braun , Bruce Lanphear , Mark J. La Guardia , Robert C. Hale , Scott Langevin , Karl Kelsey , Aimin Chen , Kimberly Yolton

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引用次数: 0

Abstract

Background

DNA methylation (DNAm) has been proposed to mediate the associations of gestational exposure to organophosphate esters (OPEs) and replacement brominated flame retardants (RBFRs) with health outcomes. However, there have not been previous epigenome-wide association studies (EWAS) on the impact of prenatal exposure to these chemicals on newborn DNAm.

Methods

In 252 pregnant women recruited to the Health Outcomes and Measures of Environment (HOME) Study from 2003 to 2006 in Cincinnati, Ohio, we measured the house dust concentrations of 4 OPEs and 2 RBFRs at 20 weeks of gestation and 3 urinary OPE metabolites at 16 and 26 weeks of gestation and at delivery. DNAm was assessed in newborn cord blood using the Infinium MethylationEPIC BeadChip. Multiple testing was controlled for using false discovery rate (FDR) P-values <0.05 for significance.

Results

Dust tris(1,3-dichloroisopropyl) phosphate was associated with increased methylation in GUK1 (cg12796841). Dust bis(2-ethylhexyl) tetrabromophthalate was associated with decreased methylation in FAM159B (cg12662072) and increased methylation in ATXN10 (cg07527826). Dust OPEs and RBFRs were associated with differentially methylated regions (DMRs) overlapping with genes involved in parturition and emotions (OXT), embryogenesis (HOXB genes), inflammation and immunity (ALOX12), cell signaling (LRRC34), spermatogenesis (BOLL), and tumorigenesis (HOXB genes, DIP2C, RASSF9, FAM118A). Urinary OPEs were associated with DMRs overlapping with DNA repair (MACROD1), stem cell pluripotency (POU5F1) and T-cell development (TCL1A) genes.

Conclusions

Prenatal OPE and RBFR exposure is associated with altered newborn DNAm. Future studies should determine if these alterations lead to disease later in life.

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妊娠期暴露于有机磷酸酯和溴化阻燃剂与新生儿DNA甲基化的全表观基因组关联研究

dna甲基化（DNAm）已被提出介导妊娠期暴露于有机磷酸酯（OPEs）和替代溴化阻燃剂（RBFRs）与健康结果的关联。然而，目前还没有关于产前暴露于这些化学物质对新生儿dna影响的全表观基因组关联研究（EWAS）。方法在美国俄亥俄州辛辛那提市2003 - 2006年健康结局与环境测量（HOME）研究中招募的252名孕妇中，我们测量了妊娠20周时4种OPEs和2种RBFRs的室内粉尘浓度以及妊娠16周和26周及分娩时3种尿OPEs代谢物的浓度。使用Infinium MethylationEPIC BeadChip评估新生儿脐带血中的dna。多重检验采用错误发现率（FDR） p值<；0.05表示显著性。结果粉尘三磷酸（1,3-二氯异丙基）与GUK1 （cg12796841）甲基化增加相关。与FAM159B （cg12662072）甲基化降低和ATXN10 （cg07527826）甲基化升高相关。尘埃OPEs和RBFRs与差异甲基化区域（DMRs）相关，这些区域与参与分娩和情绪（OXT）、胚胎发生（HOXB基因）、炎症和免疫（ALOX12）、细胞信号传导（LRRC34）、精子发生（BOLL）和肿瘤发生（HOXB基因、DIP2C、RASSF9、FAM118A）的基因重叠。尿OPEs与DMRs与DNA修复（MACROD1）、干细胞多能性（POU5F1）和t细胞发育（TCL1A）基因重叠相关。结论产前暴露于OPE和RBFR与新生儿dna改变有关。未来的研究应该确定这些改变是否会在以后的生活中导致疾病。

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来源期刊

Science of the Total Environment 环境科学-环境科学

CiteScore

17.60

自引率

10.20%

发文量

8726

审稿时长

2.4 months

期刊介绍： The Science of the Total Environment is an international journal dedicated to scientific research on the environment and its interaction with humanity. It covers a wide range of disciplines and seeks to publish innovative, hypothesis-driven, and impactful research that explores the entire environment, including the atmosphere, lithosphere, hydrosphere, biosphere, and anthroposphere. The journal's updated Aims & Scope emphasizes the importance of interdisciplinary environmental research with broad impact. Priority is given to studies that advance fundamental understanding and explore the interconnectedness of multiple environmental spheres. Field studies are preferred, while laboratory experiments must demonstrate significant methodological advancements or mechanistic insights with direct relevance to the environment.