In Utero Exposure to Air Pollutants and Mitochondrial Heteroplasmy in Neonates

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 (PM 2.5 ) and NO 2 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 PM 2.5 and NO 2 concentrations were determined by a highresolution 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 NO 2 exposure and cord-blood mtDNA heteroplasmy. A 5 μg/m 3 increment in NO 2 was linked with MT-D-Loop 16311T>C heteroplasmy from gestational weeks 17−25. MT-CYTB 14766C>T was negatively associated with NO 2 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 PM 2.5 exposure. This is the first study to show that prenatal NO 2 exposure is associated with cord-blood mitochondrial mutations and suggests two critical windows of exposure in mid-to-late pregnancy.

Exploring Mitochondrial Heteroplasmy in Neonates: Implications for Growth Patterns in the First Years of Life

“…These changes can contribute to the storage of excess calories, predisposing children to develop overweight or obesity (31). For instance, prenatal air pollution exposure was linked with changes in cord blood mtDNA heteroplasmy levels (13,19), of which cord blood MT-ND4L 10550A > G heteroplasmy was found to be positively associated with childhood overweight at four to six years (13).…”

“…Within the framework of the ongoing prospective birth cohort 'Environmental In uence on Aging in Early Life' (ENVIRONAGE; Flanders, Belgium) (18), we included 200 mother-child pairs recruited between February 2010 and September 2013 (19) (Supplementary Figure S1). Details on the study protocol have been described previously (18).…”

“…Whole mitochondrial genome sequencing was performed by Macrogen Europe, as described elsewhere (19). Demultiplexed fastq les were used for downstream analyses, which were performed with Geneious Prime (version 2021.2.2).…”

“…Estimates were provided as OR with 95% CI of developing rapid growth per unit increase in cord blood mtDNA content. Principal component analysis was performed to determine the degree of correlation between the detected SNPs (19,26). To allow for making multiple comparisons while considering the degree of correlation, the effective number of tests based on principal component analysis was estimated.…”

Mitochondrial DNA heteroplasmy analysis in keratoconus patients from China

“…The ratio of the mutant allele was used to represent the heteroplasmic level. As previously recommended ( Cosemans et al, 2023 ), only heteroplasmic variants with a prevalence of at least 10% in the study population were included for further analysis.…”