Everson Todd M, Sehgal Neha, Campbell Kyle, Barr Dana Boyd, Panuwet Parinya, Yakimavets Volha, Chen Kelsey, Perez Cynthia, Shankar Kartik, Eick Stephanie M, Pearson Kevin J, Andres Aline
Gangarosa Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, USA; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Gangarosa Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Environ Pollut. 2025 Mar 1;368:125737. doi: 10.1016/j.envpol.2025.125737. Epub 2025 Jan 23.
The placenta is crucial for fetal development, is affected by PFAS toxicity, and evidence is accumulating that gestational PFAS perturb the epigenetic activity of the placenta. Gestational PFAS exposure can adversely affect offspring, yet individual and cumulative impacts of PFAS on the placental epigenome remain underexplored. Here, we conducted an epigenome-wide association study (EWAS) to examine the relationships between placental PFAS levels and DNA methylation in a cohort of mother-infant dyads in Arkansas (N = 151). We measured 17 PFAS in human placental tissues and quantified placental DNA methylation levels via the Illumina EPIC Microarray. We tested for differential DNA methylation with individual PFAS, and with mixtures of multiple PFAS. Our results demonstrated that numerous epigenetic loci were perturbed by PFAS, with PFHxS exhibiting the most abundant effects. Mixture analyses suggested cumulative effects of PFOA and PFOS, while PFHxS may act more independently. We additionally explored whether sex-specific effects may be present and concluded that future large studies should explicitly test for sex-specific effects. The genes that are annotated to our PFAS-associated epigenetic loci are primarily involved in growth processes and cardiometabolic health, while some genes are involved in neurodevelopment. These findings shed light on how prenatal PFAS exposures affect birth outcomes and children's health, emphasizing the importance of understanding PFAS mechanisms in the in-utero environment.
胎盘对胎儿发育至关重要，会受到全氟辛烷磺酸毒性的影响，并且越来越多的证据表明孕期接触全氟辛烷磺酸会扰乱胎盘的表观遗传活性。孕期接触全氟辛烷磺酸会对后代产生不利影响，然而全氟辛烷磺酸对胎盘表观基因组的个体和累积影响仍未得到充分研究。在此，我们进行了一项全表观基因组关联研究（EWAS），以检验阿肯色州一组母婴二元组（N = 151）中胎盘全氟辛烷磺酸水平与DNA甲基化之间的关系。我们测量了人胎盘组织中的17种全氟辛烷磺酸，并通过Illumina EPIC微阵列对胎盘DNA甲基化水平进行了定量。我们测试了单个全氟辛烷磺酸以及多种全氟辛烷磺酸混合物导致的DNA甲基化差异。我们的结果表明，许多表观遗传位点受到全氟辛烷磺酸的干扰，其中全氟己烷磺酸的影响最为显著。混合物分析表明全氟辛酸和全氟辛烷磺酸具有累积效应，而全氟己烷磺酸可能发挥更独立的作用。我们还探讨了是否可能存在性别特异性影响，并得出结论，未来的大型研究应明确测试性别特异性影响。与我们的全氟辛烷磺酸相关表观遗传位点相关的基因主要参与生长过程和心脏代谢健康，而一些基因则参与神经发育。这些发现揭示了产前接触全氟辛烷磺酸如何影响出生结局和儿童健康，强调了理解子宫内环境中全氟辛烷磺酸作用机制的重要性。
