Placental PFAS concentrations are associated with perturbations of placental DNA methylation

Authors: EVERSON, TODD - Emory University; SEHGAL, NEHA - Emory University; CAMPBELL, KYLE - Emory University; BOYD BARR, DANA - Emory University; PANUWET, PARINYA - Emory University; YAKIMAVETS, VOLHA - Emory University; CHEN, KELSEY - Emory University; PEREZ, CYNTHIA - Emory University; EICK, STEPHANIE - Emory University; Shankar, Kartik; PEARSON, KEVIN - University Of Kentucky; ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Environmental Pollution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/21/2025
Publication Date: 1/23/2025
Citation: Everson, T., Sehgal, N., Campbell, K., Boyd Barr, D., Panuwet, P., Yakimavets, V., Chen, K., Perez, C., Eick, S.M., Shankar, K., Pearson, K., Andres, A. 2025. Placental PFAS concentrations are associated with perturbations of placental DNA methylation. Environmental Pollution. 368(2025). Article 125735. https://doi.org/10.1016/j.envpol.2025.125737.
DOI: https://doi.org/10.1016/j.envpol.2025.125737

Interpretive Summary: The placenta is an important organ during pregnancy because it helps the baby grow and develop. Scientists are learning that certain man-made chemicals in the environment, called PFAS (per- and polyfluoroalkyl substances), can modify how the placenta works. These chemicals are found in everyday products like non-stick cookware, water-resistant clothing, and food packaging, and they can stay in the body for a long time. This study looked at how PFAS might change the activity of genes in the placenta by altering a process called DNA methylation, a way genes are turned on or off. Researchers studied placentas from 151 moms and babies in Arkansas. They measured 17 different PFAS chemicals and looked for changes in the placenta genes. They found that many gene changes were associated with PFAS exposure, especially one chemical called PFHxS. These changes in the placenta were connected to genes involved in growth, heart health, and brain development. The results suggest that being exposed to PFAS during pregnancy could impact how babies grow and develop. It also highlights the need for more research, especially to see if the effects are different for boys and girls.

Technical Abstract: 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 PFHx 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.