Maternal PM2.5 exposure is associated with preterm birth and gestational diabetes mellitus, and mitochondrial OXPHOS dysfunction in cord blood

Abstract

Maternal exposure to fine particulate matter (PM2.5) is associated with adverse pregnancy and neonatal health outcomes. To explore the mechanism, we performed mRNA sequencing of neonatal cord blood. From an ongoing prospective cohort, Air Pollution on Pregnancy Outcome (APPO) study, 454 pregnant women from six centers between January 2021 and June 2022 were recruited. Individual PM2.5 exposure was calculated using a time-weighted average model. In the APPO study, age-matched cord blood samples from the High PM2.5 ((>)15 ug/m(3); n = 10) and Low PM2.5 (<= 15 ug/m(3); n = 30) groups were randomly selected for mRNA sequencing. After selecting genes with differential expression in the two groups (p-value < 0.05 and log2 fold change > 1.5), pathway enrichment analysis was performed, and the mitochondrial pathway was analyzed using MitoCarta3.0. The risk of preterm birth (PTB) increased with every 5 mu g/m(3) increase of PM2.5 in the second trimester (odds ratio 1.391, p = 0.019) after adjusting for confounding variables. The risk of gestational diabetes mellitus (GDM) increased in the second (odds ratio 1.238, p = 0.041) and third trimester (odds ratio 1.290, p = 0.029), and entire pregnancy (odds ratio 1.295, p = 0.029). The mRNA-sequencing of cord blood showed that genes related to mitochondrial activity (FAM210B, KRT1, FOXO4, TRIM58, and FBXO7) and PTB-related genes (ADIPOR1, YBX1, OPTN, NFkB1, HBG2) were upregulated in the High PM2.5 group. In addition, exposure to high PM2.5 affected mitochondrial oxidative phosphorylation (OXPHOS) and proteins in the electron transport chain, a subunit of OXPHOS. These results suggest that exposure to high PM2.5 during pregnancy may increase the risk of PTB and GDM, and dysregulate PTB-related genes. Alterations in mitochondrial OXPHOS by high PM2.5 exposure may occur not only in preterm infants but also in normal newborns. Further studies with larger sample sizes are required.