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Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIR ON AGE birth cohort study
Open accessAbstract
Most research to date has focused on epigenetic modifications in the nuclear genome, with little attention devoted to mitochondrial DNA (mtDNA). Placental mtDNA content has been shown to respond to environmental exposures that induce oxidative stress, including airborne particulate matter (PM). Damaged or non-functioning mitochondria are specifically degraded through mitophagy, exemplified by lower mtDNA content, and could be primed by epigenetic modifications in the mtDNA. We studied placental mtDNA methylation in the context of the early life exposome. We investigated placental tissue from 381 mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. We determined mtDNA methylation by bisulfite-pyrosequencing in 2 regions, i.e., the D-loop control region and 12S rRNA (MT-RNR1), and measured mtDNA content by qPCR. PM2.5 exposure was calculated for each participant's home address using a dispersion model. An interquartile range (IQR) increment in PM2.5 exposure over the entire pregnancy was positively associated with mtDNA methylation (MT-RNR1: +0.91%, P = 0.01 and D-loop: +0.21%, P = 0.05) and inversely associated with mtDNA content (relative change of -15.60%, P = 0.001) in placental tissue. mtDNA methylation was estimated to mediate 54% [P = 0.01 (MT-RNR1)] and 27% [P = 0.06 (D-loop)] of the inverse association between PM2.5 exposure and mtDNA content. This study provides new insight into the mechanisms of altered mitochondrial function in the early life environment. Epigenetic modifications in the mitochondrial genome, especially in the MT-RNR1 region, substantially mediate the association between PM2.5 exposure during gestation and placental mtDNA content, which could reflect signs of mitophagy and mitochondrial death.
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![Figure 3. Estimated proportion of effects of PM2.5 exposure during gestation on mtDNA content mediated through changes in mtDNA methylation. The figure displays placental mtDNA methylation as mediator [(A) MT-RNR1; (B) D-loop], the estimates of indirect effect (IE), the estimates of the direct effect (DE), and proportion of mediation (IE/DE+IE). The effects are relative changes in placental mtDNA content for an IQR increment of PM2.5 exposure. The mediation model was adjusted for gender, age, gestational age, smoking, maternal education, parity, ethnicity, and season at conception.](/paper-figures/f0e318b82af24f168ea47e9052042750/placental-mitochondrial-methylation-and-exposure-to-airborne-particulate-matter-figure-3.jpg)
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“Furthermore, mtDNA methylation is disturbed by environmental and other factors, such as traffic-derived elemental carbon105, maternal smoking106, endogenous metabolites107, cell senescence108 and ageing109.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [105]
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“Janssen et al. [192] reported in utero exposure to PM2.5 led to lower mtDNA content (as described in the section on oxidative stress), as well as modified the methylation level in the MT-RNR1 region.”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [192]
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“Last, epigenetic modifications in placental mtDNA have been correlated with PM2.5 exposure.”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [192]
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Metadata
- Authors
- Janssen, B. G., Byun, H.-M., Gyselaers, W., Lefebvre, W., Baccarelli, A. A., & Nawrot, T. S.
- Affiliations
- Hasselt University (BE)
- Harvard University (US)
- Ziekenhuis Oost-Limburg (BE)
- Flemish Institute for Technological Research (BE)
- Corresponding author
- Nawrot, Tim S
- ORCID
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2015-05-21
- Volume
- 10
- Issue
- 6
- Pages
- 536-544
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC4623402
- OpenAlex
- W1828742533
- Cited by
- 187
- References
- 45
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 17 · 2023: 13 · 2022: 23 · 2021: 18 · 2020: 18 · 2019: 15 · 2018: 23 · 2017: 25 · 2016: 15 · 2015: 2
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Epigenetics (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Document Server@UHasselt (UHasselt) (submittedVersion, cc-by-nc)
- Lirias (submittedVersion)
- Funders
- National Institute of Environmental Health Sciences (R21ES022694, R01ES021733, R01ES021357)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- PM2.5 exposure, airborne particulate matter, mtDNA content, mitophagy, MT-RNR1, D-loop, oxidative stress, ENVIRONAGE birth cohort, mediation analysis
- MeSH terms
- Environmental Exposure, Female, Humans, Infant, Newborn, Male, Mitochondria, Placenta, Pregnancy, RNA, Ribosomal, Oxidative Stress, DNA Methylation, Epigenesis, Genetic, Particulate Matter, Genome, Mitochondrial
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