Abstract
BACKGROUND: Prenatal ambient fine particulate matter (PM(2.5)) and maternal chronic psychosocial stress have independently been linked to changes in mithochondrial DNA copy number (mtDNAcn), a marker of mitochondrial response and dysfunction. Further, overlapping research shows sex-specific effects of PM(2.5) and stress on developmental outcomes. Interactions among PM(2.5), maternal stress, and child sex have not been examined in this context. METHODS: We examined associations among exposure to prenatal PM(2.5), maternal lifetime traumatic stressors, and mtDNAcn at birth in a sociodemographically diverse pregnancy cohort (N=167). Mothers' daily exposure to PM(2.5) over gestation was estimated using a satellite-based spatio-temporally resolved prediction model. Lifetime exposure to traumatic stressors was ascertained using the Life Stressor Checklist-Revised; exposure was categorized as high vs. low based on a median split. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNAcn in placenta and cord blood leukocytes. Bayesian Distributed Lag Interaction regression models (BDLIMs) were used to statistically model and visualize the PM(2.5) timing-dependent pattern of associations with mtDNAcn and explore effect modification by maternal lifetime trauma and child sex. RESULTS: Increased PM(2.5) exposure across pregnancy was associated with decreased mtDNAcn in cord blood (cumulative effect estimate=-0.78; 95%CI -1.41, -0.16). Higher maternal lifetime trauma was associated with reduced mtDNAcn in placenta (β=-0.33; 95%CI -0.63, -0.02). Among women reporting low trauma, increased PM(2.5) exposure late in pregnancy (30-38weeks gestation) was significantly associated with decreased mtDNAcn in placenta; no significant association was found in the high trauma group. BDLIMs identified a significant 3-way interaction between PM(2.5), maternal trauma, and child sex. Specifically, PM(2.5) exposure between 25 and 40weeks gestation was significantly associated with increased placental mtDNAcn among boys of mothers reporting high trauma. In contrast, PM(2.5) exposure in this same window was significantly associated with decreased placental mtDNAcn among girls of mothers reporting low trauma. Similar 3-way interactive effects were observed in cord blood. CONCLUSIONS: These results indicate that joint exposure to PM(2.5) in late pregnancy and maternal lifetime trauma influence mtDNAcn at the maternal-fetal interface in a sex-specific manner. Additional studies will assist in understanding if the sex-specific patterns reflect distinct pathophysiological processes in addition to mitochondrial dysfunction.