Prenatal particulate matter exposure and mitochondrial dysfunction at the maternal-fetal interface: Effect modification by maternal lifetime trauma and child sex

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 (30–38 weeks 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 40 weeks 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.