Epigenetic mechanisms linking the perinatal environment, the placenta, and maternal and child health outcomes: evidence for sexual dimorphism

Abstract Exposure to adverse environments early in life can shape health trajectories across the lifespan. A key mechanism by which this life-long reprogramming occurs is via epigenetic modifications, including altered DNA methylation (DNAm), histone modifications, and microRNA (miRNA) regulation. This invited perspective highlights key human population studies and selected animal studies from our group and collaborators that have examined toxicant exposure occurring during or prior to pregnancy including metals, pharmaceuticals, microorganisms, air pollution, and socioeconomic stressors and their impact on the epigenome. Exposure to these substances is associated with altered epigenetic patterning in fetal blood and placenta, often in a gene- and sex-specific manner. This gene specificity may be tied to the transcription factor occupancy, where environmental exposures alter transcription factor binding at regulatory regions, influencing downstream epigenetic patterns. In relation to adverse health outcomes, these epigenetic modifications have been associated with adverse pregnancy outcomes such as preeclampsia as well as neonatal health (i.e., preterm birth, retinopathy of prematurity, chronic lung disease, and congenital heart defects). Additionally, these epigenetic alterations have been associated with outcomes later in childhood, including cognition, neurodevelopmental disorders (e.g., autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD)), obesity, metabolic dysregulation, asthma, and immune dysfunction. Collectively, these studies highlight the relationships among early-life environmental factors, epigenetic biomarkers, and maternal and child health outcomes.