In Utero Exposure to Air Pollutants and Mitochondrial Heteroplasmy in Neonates

Environ Sci Technol. 2023 Jan 10;57(1):350-359. doi: 10.1021/acs.est.2c02556. Epub 2022 Dec 14.

Abstract

Mitochondria are sensitive to oxidative stress, which can be caused by traffic-related air pollution. Placental mitochondrial DNA (mtDNA) mutations have been previously linked with air pollution. However, the relationship between prenatal air pollution and cord-blood mtDNA mutations has been poorly understood. Therefore, we hypothesized that prenatal particulate matter (PM2.5) and NO2 exposures are associated with cord-blood mtDNA heteroplasmy. As part of the ENVIRONAGE cohort, 200 mother-newborn pairs were recruited. Cord-blood mitochondrial single-nucleotide polymorphisms were identified by whole mitochondrial genome sequencing, and heteroplasmy levels were evaluated based on the variant allele frequency (VAF). Outdoor PM2.5 and NO2 concentrations were determined by a high-resolution spatial-temporal interpolation method based on the maternal residential address. Distributed lag linear models were used to determine sensitive time windows for the association between NO2 exposure and cord-blood mtDNA heteroplasmy. A 5 μg/m3 increment in NO2 was linked with MT-D-Loop16311T>C heteroplasmy from gestational weeks 17-25. MT-CYTB14766C>T was negatively associated with NO2 exposure in mid pregnancy, from weeks 14-17, and positively associated in late pregnancy, from weeks 31-36. No significant associations were observed with prenatal PM2.5 exposure. This is the first study to show that prenatal NO2 exposure is associated with cord-blood mitochondrial mutations and suggests two critical windows of exposure in mid-to-late pregnancy.

Keywords: DLM; SNP; air pollution; heteroplasmy; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants* / analysis
  • Air Pollution* / analysis
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / pharmacology
  • Environmental Exposure
  • Female
  • Heteroplasmy
  • Humans
  • Infant, Newborn
  • Maternal Exposure
  • Mitochondria / chemistry
  • Mitochondria / genetics
  • Nitrogen Dioxide
  • Particulate Matter / analysis
  • Placenta / chemistry
  • Pregnancy

Substances

  • Air Pollutants
  • Nitrogen Dioxide
  • Particulate Matter
  • DNA, Mitochondrial