Associations of prenatal exposure to NO2 and near roadway residence with placental gene expression

Abstract

BACKGROUND AND AIM: The placenta serves as a critical interface between maternal and fetal environments mediating effect of maternal environmental exposures on fetal growth and development. Traffic-related air pollution (TRAP) is a ubiquitous exposure that has been related to several adverse health outcomes. We examined associations of maternal prenatal TRAP exposure (using NO₂ and near roadway residence) and genome-wide placental gene expression. METHODS: Placental samples were collected from CANDLE (Memphis, TN) (n=776) and GAPPS (Seattle and Yakima, WA) (n=205) cohorts in the ECHO-PATHWAYS consortium. NO₂ exposure was characterized using a spatiotemporal model and separately averaged for each trimester and the first and last month of pregnancy. Confounder adjusted cohort-specific linear models were fit for 11,000 protein-coding genes and each exposure (NO₂ exposure window, linear distance and proximity 150 m to three roadway types). Offspring sex-specific associations were examined using interaction terms. False discovery rates (FDR)0.10 were used for statistical significance. RESULTS:Mean NO₂ levels were 8.2 (SD=3.2) and 7.8 (SD=3.9) ppb while mean distances to nearest roadways were 466 (SD=521) and 525 (SD=926) meters in CANDLE and GAPPS, respectively. Despite no NO₂ main effects, In GAPPS, expression of B4GALNT2 and ADGRG2 was associated with linear distance to A3 roadways (FDR p-values=0.057 and 0.096, respectively) and expression of ZFP92 (FDR p-value=0.058) was associated with close proximity to A3 roadways. Offspring sex and first trimester NO₂ interaction was observed in CANDLE for RASSF7 (interaction FDR p-value=0.067) where positive association was observed only for male infants. In GAPPS, positive association of STRIP2 expression with second trimester NO₂ was observed only among male infants (interaction FDR p-value=0.021). CONCLUSIONS:We found suggestive associations of near roadway residence with placental gene expression. Offspring sex may modify associations of NO₂ with placental expression. Identified genes play roles in cell signaling, a potential mechanism for effects of prenatal TRAP exposure on placental function. KEYWORDS: Transcriptomics, Epidemiology, Traffic-related, Air pollution