The body does not forget: Infants' epigenetic memories of the exposure to psychological stress and air pollution during pregnancy

The fetal period is known as playing a crucial role in shaping developmental trajectories, as the adaptations to the intrauterine and maternal environments lead to permanent physiological alterations in adulthood, a phenomenon that is named “fetal programming”. Consistently, evidence shows that environmental stressors during pregnancy contribute to increasing the risk for adverse birth outcomes, as well as for epigenetic alterations. For instance, the DNA methylation has been widely studied and is primarily relevant for the silencing of target genes. Among the environmental stressors that have been demonstrated in association with such epigenetic footprints, literature highlights maternal prenatal stress and air pollution exposure, frequently measured in terms of particulate matter (PM) concentration. Interestingly, while there is strong evidence in favour of the independent effect of each factor, research is still very scarce regarding a possible joint effect on DNA methylation. Therefore, we conducted a new study aimed at investigating the independent and cumulative effect of maternal pandemic-related stress (PRS) during COVID-19 outbreak and the antenatal exposure to PM2.5 on infants’ methylation levels of the gene SCL6A4, which has a pivotal role in socio-emotional regulation and is considered a potential biomarker of early adverse experiences. The findings highlighted a significant interaction effect for high levels of PRS and PM2.5 in association with the hypermethylation of six CpG sites of SCL6A4. In addition, exploratory analyses indicated the second trimester as being the period of major vulnerability to the examined stressors exposure. Overall, the study needs further replication but emphasizes the need for a multi-level approach in this field of research, in order to better understand the interplay between environmental and individual-level stressors and ultimately improve mother-infant health. Key words: fetal programming; epigenetic footprints; DNA methylation; maternal prenatal stress; pollution; COVID-19; PM2.5; SCL6A4