Gestational Exposure to Bisphenols and Perceived Stress Predict DNA Methylation Changes in Mothers and Newborn Infants

Abstract

Bisphenols, including bisphenol A and “bisphenol A–free” substitute chemicals (e.g., bisphenol S, bisphenol F), are often used in the manufacture of water bottles, food storage containers, the lining of tin cans, and thermal paper. Gestational exposure to bisphenols has been associated with poor neurodevelopmental and mental health outcomes in children that are often sex-specific. Moreover, there is often a co-occurrence of chemical exposures and chronic stress, such that individuals living in the context of economic disadvantage and associated chronic stress often bear the burden of elevated chemical exposures. Changes in DNA methylation (DNAm) in response to environmental exposures are thought to be a prominent biological mechanism through which perinatal exposures impact neurodevelopment. We examined the associations between patterns of gestational bisphenol concentrations in third-trimester urine samples as well as maternal perceived stress and buccal cell DNAm in candidate genes involved with hypothalamic-pituitary-adrenal axis functioning (BDNF, FKBP5, NR3C1, OXTR, SLC6A4) in both mothers (n = 71–141) and newborn infants (n = 54–136) from a longitudinal birth cohort. Bisphenol urinary biomarkers and patterns were associated with maternal DNAm and sex-specific effects on newborn infant DNAm, with stronger effects in male compared with female infants. Further, maternal perceived stress during pregnancy potentiated the impacts of gestational bisphenol exposure on maternal DNAm within the SLC6A4 gene. This effect was not observed when examining infant DNAm. Maternal perceived stress during pregnancy was associated with changes in maternal and infant DNAm that were generally distinct from the effects of bisphenol exposure. These results suggest that bisphenol mixtures may be exerting biological effects that are distinct from the effects of the individual bisphenols and highlight the importance of considering multiple early-life exposures in interpreting changes in DNAm.