Associations of prenatal exposure to NO and near roadway residence with placental gene expression.

Introduction: Traffic-related air pollution (TRAP), a common exposure, potentially impacts pregnancy through altered placental function. We investigated associations between prenatal TRAP exposure and placental gene expression.

Methods: Whole transcriptome sequencing was performed on placental samples from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle and Yakima, WA) (n = 205), cohorts of the ECHO-PATHWAYS Consortium. Residential NO exposures were computed via spatiotemporal models for full-pregnancy, each trimester, and the first/last months of pregnancy. Individual cohort-specific, covariate-adjusted linear models were fit for 10,855 genes and respective exposures (NO or roadway proximity [≤150 m]). Infant-sex/exposure interactions on placental gene expression were tested with interaction terms in separate models. Significance was based on false discovery rate (FDR<0.10).

Results: In GAPPS, final-month NO exposure was positively associated with MAP1LC3C expression (FDR p-value = 0.094). Infant-sex interacted with second-trimester NO on STRIP2 expression (FDR interaction p-value = 0.011, inverse and positive associations among male and female infants, respectively) and roadway proximity on CEBPA expression (FDR interaction p-value = 0.045, inverse among females). In CANDLE, infant-sex interacted with first-trimester and full-pregnancy NO on RASSF7 expression (FDR interaction p-values = 0.067 and 0.013, respectively, positive among male infants and inverse among female infants).

Discussion: Overall, pregnancy NO exposure and placental gene expression associations were primarily null, with exception of final month NO exposure and placental MAP1LC3C association. We found several interactions of infant sex and TRAP exposures on placental expression of STRIP2, CEBPA, and RASSF7. These highlighted genes suggest influence of TRAP on placental cell proliferation, autophagy, and growth, though additional replication and functional studies are required for validation.