EV-miRNA associated with environmental air pollution exposures in the MADRES cohort

Abstract

Air pollution is a hazardous contaminant, exposure to which has substantial consequences for health during critical periods, such as pregnancy. MicroRNA (miRNA) are an epigenetic mechanism that modulates transcriptome responses to the environment and have been found to change in reaction to air pollution exposure. The data are limited regarding extracellular-vesicle (EV) miRNA variation associated with air pollution exposure during pregnancy and in susceptible populations who may be disproportionately exposed. This study aimed to identify EV-miRNA expression associated with ambient, residential exposure to PM2.5, PM10, NO2, O3 and with traffic-related NOx in 461 participants of the MADRES cohort, a low income, predominantly Hispanic pregnancy cohort based in Los Angeles, CA. This study used residence-based modeled air pollution data as well as Nanostring panels for EVmiRNA extracted with Qiagen exoRNeasy kits to evaluate 483 miRNA in plasma in early and late pregnancy. Average air pollution exposures were considered separately for 1-day, 1-week and 8-week windows before blood collection in both early and late pregnancy. This study identified 63 and 66 EV-miRNA significantly associated with PM2.5 and PM10, respectively, and 2 miRNA associated with traffic-related NOX (FDR-adjusted p-value<0.05). Of 103 unique EV-miRNA associated with PM, 92% were associated with lung conditions according to HMDD (Human miRNA Disease Database) evidence. In particular, EV-miRNA previously identified with air pollution exposure also associated with PM2.5 and PM10 in this study were: miR-126, miR-16-5p, miR-187-3p, miR200b-3p, miR486-3p, and miR-582-3p. There were no significant differences in average exposures in early vs late pregnancy. Significant EV-miRNA were only identified in late pregnancy with an eight-week exposure window, suggesting a vulnerable timeframe of exposure, rather than an acute response. These results describe a wide array of EV-miRNA for which expression is affected by PM exposure and may be in part mediating the biological response to ambient air pollution, with potential for health implications in pregnant women and their children.