Placental PFAS concentrations are associated with perturbations of placental DNA methylation

Area of Science:

• Environmental Epigenetics
• Toxicology
• Perinatal Health

Background:

• Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants linked to adverse offspring outcomes.
• Gestational PFAS exposure is known to affect placental epigenetic activity, but impacts on the placental epigenome are underexplored.
• Understanding these epigenetic changes is crucial for assessing risks to fetal development and child health.

Purpose of the Study:

• To investigate the association between placental PFAS levels and DNA methylation.
• To examine individual and cumulative effects of PFAS on the placental epigenome.
• To identify genes and pathways affected by gestational PFAS exposure.

Main Methods:

• Conducted an epigenome-wide association study (EWAS) in 151 mother-infant dyads.
• Measured 17 PFAS in placental tissues and quantified DNA methylation using the Illumina EPIC Microarray.
• Analyzed differential methylation for individual PFAS and mixtures, exploring potential sex-specific effects.

Main Results:

• Numerous epigenetic loci were perturbed by PFAS, with PFHxS showing the most significant effects.
• Mixture analyses indicated cumulative impacts of PFOA and PFOS, while PFHxS appeared to act more independently.
• PFAS-associated epigenetic loci were linked to genes involved in growth, cardiometabolic health, and neurodevelopment.

Conclusions:

• Gestational PFAS exposure significantly alters placental DNA methylation patterns.
• PFAS exposure, both individually and cumulatively, can impact genes critical for fetal development and long-term health.
• Further research, including studies on sex-specific effects, is needed to fully elucidate PFAS mechanisms in utero.