Abstract
BACKGROUND: While strong evidence supports adverse maternal and offspring consequences of air pollution, mechanisms that involve the placenta, a key part of the intrauterine environment, are largely unknown. Previous studies of air pollution and placental gene expression were small candidate gene studies that rarely considered prenatal windows of exposure or the potential role of offspring sex. We examined overall and sex-specific associations of prenatal exposure to fine particulate matter (PM(2.5)) with genome-wide placental gene expression. METHODS: Participants with placenta samples, collected at birth, and childhood health outcomes from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle, WA) (n = 205) cohorts of the ECHO-PATHWAYS Consortium were included in this study. PM(2.5) exposures during trimesters 1, 2, 3, and the first and last months of pregnancy, were estimated using a spatiotemporal model. Cohort-specific linear adjusted models were fit for each exposure window and expression of >11,000 protein coding genes from paired end RNA sequencing data. Models with interaction terms were used to examine PM(2.5)-offspring sex interactions. False discovery rate (FDR < 0.10) was used to correct for multiple testing. RESULTS: Mean PM(2.5) estimate was 10.5-10.7 μg/m(3) for CANDLE and 6.0-6.3 μg/m(3) for GAPPS participants. In CANDLE, expression of 13 (11 upregulated and 2 downregulated), 20 (11 upregulated and 9 downregulated) and 3 (2 upregulated and 1 downregulated) genes was associated with PM(2.5) in the first trimester, second trimester, and first month, respectively. While we did not find any statistically significant association, overall, between PM(2.5) and gene expression in GAPPS, we found offspring sex and first month PM(2.5) interaction for DDHD1 expression (positive association among males and inverse association among females). We did not observe PM(2.5) and offspring sex interactions in CANDLE. CONCLUSION: In CANDLE, but not GAPPS, we found that prenatal PM(2.5) exposure during the first half of pregnancy is associated with placental gene expression.