Sex-Specific Influence of Gestational PM2.5 Exposure on Placental Metabolic Gene Expression within the Rhode Island Child Health Study (RICHS)

Abstract

BACKGROUND AND AIM: Gestational exposure to ambient PM2.5 contributes to adverse metabolic health outcomes. Given the importance of the placenta in determining fetal growth and its potential to influence metabolic health outcomes in later life, we explored the influence of estimated ambient PM2.5 on placental metabolism in an infant sex-specific manner within the Rhode Island Child Health Study (RICHS). METHODS: Using Gene Ontology annotations, we identified 657 genes related to lipid and/or glucose metabolism. We first used existing RNA-Seq data on gene expression from the placentas of 148 term births to identify those genes whose expression was associated with PM2.5. We then validated the findings from this first stage using RT-PCR in placental samples from an additional 267 term births. Associations between pregnancy average PM2.5 levels and gene expression were quantified using linear regressions, overall and stratified by infant sex. RESULTS:PM2.5 was associated with expression of 32 genes (FDR 0.1) related to lipid or glucose metabolism, 24 of which exhibited sex-specific associations. We selected 5 genes ({ABHD3, ATP11A, PSCA, CLTCL1} and {ST6GALNAC4}) for validation via RT-PCR in a separate sample. PM2.5 was associated with expression of four of these genes ({ABHD3, ATP11A, PSCA} and {ST6GALNAC4}). In sex-stratified analyses, we found that PM2.5 was associated with {ABHD3, ATP11A} and {PSCA} in male infants only, while {ST6GALNAC4} showed no sex dependency. CONCLUSIONS:Placental metabolic gene expression was associated with PM2.5 levels during pregnancy, were over-represented for genes involved in lipid metabolism and demonstrated stronger associations in male infants. [NIH-NIEHS Funding: {P30ES023515, P30ES109776; R24ES028507, 2T32ES007324-16}]. KEYWORDS: PM2.5, placenta, metabolism, sex, pregnancy