Prenatal exposure to per- and polyfluoroalkyl substances and DNA methylation in the placenta: A prospective cohort study

Xie, Zhenzhen; Sun, Songlin; Ji, Honglei; Miao, Maohua; He, Wanhong; Song, Xiuxia; Cao, Wencheng; Wu, Qihan; Liang, Hong; Yuan, Wei

doi:10.1016/j.jhazmat.2023.132845

Cited by 2 publications

(1 citation statement)

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“…Another study examined relationships between maternal plasma PFAS concentrations with placental DNAm differences using reduced representation bisulfite sequencing in a sub-sample (n=16), then demonstrated more statistically robust associations with three of these five candidates in the full cohort (n=345) [10]. Thus, to date, studies of the impacts of gestational PFAS exposure on the human placental methylome have primarily utilized maternal plasma as an exposure biomarker, or when placental PFAS levels were quantified, they were only examined in association with targeted genes and features.…”

Section: Introductionmentioning

confidence: 99%

Placental PFAS concentrations are associated with perturbations of placental DNA methylation at loci with important roles on cardiometabolic health

Everson,

Sehgal,

Barr

et al. 2024

Preprint

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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 is 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. 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.

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Section: Introductionmentioning

confidence: 99%