Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM2.5 exposure

Abstract

Background: Exposure to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM2.5) can affect birth outcomes through physiological pathways such as inflammation. One potential way PM2.5 affects physiology could be through altering DNA methylation (DNAm). Considering that exposures during specific windows of gestation may have unique effects on DNAm, we hypothesized a timing-specific association between PM2.5 exposure during pregnancy and DNAm in the neonatal epithelial-cell epigenome. Methods: After collecting salivary samples from a cohort of 91 neonates, DNAm was assessed at over 850,000 cytosine-guanine dinucleotide (CpG) methylation sites on the epigenome using the MethylationEPIC array. Daily ambient PM2.5 concentrations were estimated based on the mother’s address of primary residence during pregnancy. PM2.5 was averaged over the first two trimesters, separately and combined, and tested for association with DNAm through an epigenome-wide association (EWA) analysis. For each EWA, false discovery rate (FDR)-corrected P < 0.05 constituted a significant finding and every CpG site with uncorrected P < 0.0001 was selected to undergo pathway and network analysis to identify molecular functions enriched by them. Results: Our analysis showed that cg18705808 was associated with the combined average of PM2.5. Pathway and network analysis revealed little similarity between the first two trimesters. Previous studies reported that TMEM184A, the gene regulated by cg18705808, has a putative role in inflammatory pathways. Conclusions: The differences in pathway and network analyses could potentially indicate trimester-specific effects of PM2.5 on DNAm. Further analysis with greater temporal resolution would be valuable to fully characterize the effect of PM2.5 on DNAm and child development.

Advances in respiratory physiology in mouse models of experimental asthma

“…In this scenario, PM exposure can initially cause changes in maternal DNA methylation ( Ferrari et al, 2019 ) that are then inherited by the offspring, which could explain why migrating to a pollutant-free area during pregnancy is not sufficient to mitigate the risk of asthma development in offspring ( Wang et al, 2021b ). Additionally, epigenetic modifications to the fetal genome during in utero PM exposure can further increase the risk of asthma, such as the antioxidant superoxide dismutase 2 (SOD2) promoter DNA methylation, and TMEM184A which is involved in the inflammatory response ( Zhou et al, 2019 ; Parikh et al, 2022 ). In summary, maternal exposure to inhaled toxins, such as tobacco smoke and PMs, can increase the risk of asthma in offspring via multiple mechanisms, including impaired lung development and structure, oxidative stress, immune response, and epigenetic modifications.…”