Newborn sex-specific transcriptome signatures and gestational exposure to fine particles: findings from the ENVIRONAGE birth cohort

Abstract

Background: Air pollution exposure during pregnancy has been associated with adverse birth outcomes and health problems later in life. We investigated sex-specific transcriptomic responses to gestational long- and short-term exposure to particulate matter with a diameter < 2.5 μm (PM_2.5) in order to elucidate potential underlying mechanisms of action.

Methods: Whole genome gene expression was investigated in cord blood of 142 mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. Daily PM_2.5 exposure levels were calculated for each mother's home address using a spatial-temporal interpolation model in combination with a dispersion model to estimate both long- (annual average before delivery) and short- (last month of pregnancy) term exposure. We explored the association between gene expression levels and PM_2.5 exposure, and identified modulated pathways by overrepresentation analysis and gene set enrichment analysis.

Results: Some processes were altered in both sexes for long- (e.g. DNA damage) or short-term exposure (e.g. olfactory signaling). For long-term exposure in boys neurodevelopment and RhoA pathways were modulated, while in girls defensin expression was down-regulated. For short-term exposure we identified pathways related to synaptic transmission and mitochondrial function (boys) and immune response (girls).

Conclusions: This is the first whole genome gene expression study in cord blood to identify sex-specific pathways altered by PM_2.5. The identified transcriptome pathways could provide new molecular insights as to the interaction pattern of early life PM_2.5 exposure with the biological development of the fetus.

Keywords: Ambient air pollution; Fetal; Microarray analysis; Particulate matter; Sex.