Prenatal exposure to environmental air pollution and psychosocial stress jointly contribute to the epigenetic regulation of the serotonin transporter gene in newborns

Abstract

Abstract Antenatal exposures to maternal stress and to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) have been independently associated with developmental outcomes in early infancy and beyond. Knowledge about their joint impact, as well as possible biological mechanisms of their effects, is still limited. Both PM2.5 and maternal stress exposure during pregnancy might result in altered patterns of DNA methylation in specific stress-related genes, such as the serotonin transporter gene (SLC6A4 DNAm), that might, in turn, influence infant development. Here, we investigated the independent and interactive influence of variations in antenatal exposures to maternal pandemic-related stress (PRS) and PM2.5 on SLC6A4 DNAm levels in newborns. Mother–infant dyads (N=307) were enrolled at delivery during the COVID-19 pandemic. Infants’ methylation status was assessed in 13 CpG sites within the SLC6A4 gene’s region (chr17:28562750–28562958) in buccal cells at birth and women retrospectively report on PRS. PM2.5 exposure over gestation and at each gestational trimester was estimated using a spatiotemporal model based on residential address. Higher levels of SLC6A4 DNAm at 6 CpG sites were found in newborns born to mothers reporting higher levels of antenatal PRS and greater PM2.5 exposure across gestation, while adjusting for infant’s sex. These effects were especially evident when exposure to elevated PM2.5 occurred during the second trimester of pregnancy. Understanding the interplay between environmental and individual-level stressors has important implications for the improvement of mother-infant health during and after the pandemic.