Placental DNA hypomethylation in association with particulate air pollution in early life

摘要

Background: There is evidence that altered DNA methylation is an important epigenetic mechanism in prenatal programming and that developmental periods are sensitive to environmental stressors.Aims: We hypothesized that exposure to fine particles (PM2.5) during pregnancy could influence DNA methylation patterns of the placenta.Methods: In the ENVIRONAGE birth cohort, levels of 5'-methyl-deoxycytidine (5-mdC) and deoxycytidine (dC) were quantified in placental DNA from 240 newborns. Multiple regression models were used to study placental global methylation and in utero exposure to PM2.5 over various time windows during pregnancy.Results: PM2.5 exposure during pregnancy averaged (25th-75th percentile) 17.2 (15.3-19.1) μg/m3. Placental global DNA methylation was inversely associated with PM2.5 exposures during whole pregnancy and decreased by 1.94% (95% confidence interval (CI): -3.88, -0.01%, p = 0.05) for each 5 μg/m~3 increase in exposure to PM2.5. The corresponding trimester specific estimate was -1.80% (95% CI: -3.26, -0.35%, p = 0.016) for the first trimester, while no significant association was observed with PM2.5 exposure of the second trimester (-0.92%, 95% CI: -2.35, 0.50%, p = 0.21) and the third trimester (-0.88%, 95% CI: -2.16, 0.39%, p = 0.18). When we analyzed smaller time windows of exposure within trimester 1, we observed a lower placental methylation at birth of-1.53% (95% CI: -2.45, -0.23%, p = 0.0012) and -1.22 % (95% CI: -1.91, -0.52%, p = 0.0008) for each 5 μg/m~3 higher PM2.5 exposure during the implantation stage and the post-implantation stage respectively.Conclusions: We observed a lower degree of global placental methylation in association with exposure to particulate air pollution in early pregnancy. Moreover, we show that global DNA methylation is affected during the critical stages of implantation. Future studies should elucidate genome-wide and gene-specific methylation patterns in placental tissue that could link particulate exposure during in utero life and early epigenetic modulations.