2594

Introduction: Exposure to ambient fine particulate matter (PM2.5) is linked to changes in placental mitochondrial DNA (mtDNA) copy number. Whether PM2.5 impacts mitochondrial mutational load in placental tissue-another biomarker of oxidative damage and aging has not been studied. Further, genetic ancestry likely impacts this relationship and may inform health disparities. Methods: We examine the association between PM2.5 and placental mtDNA mutational load in an urban multi-ethnic cohort (N=285). Mothers' daily exposure to PM2.5 over gestation was estimated using a satellite-based spatio-temporally resolved prediction model. Whole mtDNA sequencing was performed and mutations and haplogroups were determined. Bayesian Distributed Lag Interaction regression models (BDLIMs) were used to statistically model and visualize the PM2.5 timing-dependent pattern of associations with mtDNA mutations (total load and gene-specific) and explore effect modification by haplogroup. Results: Overall, increased PM2.5 exposure across pregnancy was not associated with total mutational load. However, results varied by mtDNA haplogroup with increases in PM2.5 being associated with higher total mutational load for African (cumulative effect 1.92, 95%CI 0.46, 3.48) and Asian (cumulative effect: 1.33, 95% CI 0.07, 2.73) haplogroups; a critical window was identified between 29 and 35 weeks gestation for African haplogroups only. Gene-wise analyses suggested that increased PM2.5 exposure during mid pregnancy (20-25 weeks) might have a stronger impact on mutations located in genes coding for ATP synthase subunits regardless of haplogroup. Conclusions: Placental mtDNA mutations, associated with increased PM2.5 exposure mid to late pregnancy, may have consequences on placental energy production, aging, and metabolic regulation that may impact offspring development. Understanding how these associations differ based on ancestry may further elucidate the etiology of environmentally-related disease disparities.