Prenatal Exposure to Particulate Matter and Placental Gene Expression

Abstract

Background/Aim: Previous studies of air pollution and placental gene expression were small, candidate gene studies. Further, few considered prenatal windows of exposure and the role of offspring sex. We examined overall and sex-specific associations of prenatal maternal exposure to fine particulate matter (PM2.5) with genome-wide placental gene expression. Methods: Participants with placenta samples and childhood health outcomes from the CANDLE (Memphis, TN) (n=428) and GAPPS (Seattle, WA) (n=114) cohorts of the ECHO PATHWAYS Consortium were included. Exposures to PM2.5 during trimesters 1, 2, 3, and, the first and last months of pregnancy were estimated using a spatiotemporal model. Cohort-specific linear models were fit for each exposure window and individual gene expression (>11,000 coding genes) from paired end RNA sequencing data, adjusted for batch, age, race, offspring sex, season, calendar year of birth, gestational age, mode of delivery, presence/absence of labor, smoking, education, and pre-pregnancy obesity. Models with interaction terms were used to examine sex-specific associations. A false discovery rate (FDR<0.10) was used to correct for multiple testing. Results: Average maternal age and gestational age at delivery were 31-32 years and 38 weeks, respectively. In CANDLE, expression of 41 genes (including SCUBE2, PAEP, PGR, and DKK1) was associated with PM2.5 in the first month of pregnancy while expression of YIPF5 was associated with PM2.5 in the final month of pregnancy. In GAPPS, expression of NBPF9 and IGFBP1 was associated with PM2.5 in the final month of the pregnancy. Offspring sex and third trimester PM2.5 exposure interactions were observed for 29 genes (including ETNK2, CRIM1, and VPS35) in CANDLE and two genes (MARCO and HAPLN3) in GAPPS. Conclusions: We found evidence suggesting association between prenatal PM2.5 exposure, particularly during early and late pregnancy, and placental gene expression (including genes involved in signaling and hormone metabolism). Child sex may modify the association.