Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIRONAGE birth cohort study
| Autor: | Hyang-Min Byun, Bram G. Janssen, Wouter Lefebvre, Andrea A. Baccarelli, Tim S. Nawrot, Wilfried Gyselaers |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Mitochondrial DNA mitochondrial DNA content placenta air pollution Context (language use) 010501 environmental sciences Mitochondrion Biology 01 natural sciences Epigenesis Genetic Andrology DNA methylation epigenetics mitochondria mitochondrial DNA methylation particulate matter 03 medical and health sciences Pregnancy Placenta Mitophagy medicine Humans Epigenetics Molecular Biology 030304 developmental biology 0105 earth and related environmental sciences Genetics 0303 health sciences Infant Newborn Methylation Environmental Exposure Mitochondria Oxidative Stress medicine.anatomical_structure 13. Climate action RNA Ribosomal Genome Mitochondrial Female mtDNMT1 Mitochondrial isoform of nuclear-encoded DNA methyltransferase enzyme 1 MT-RNR1 Mitochondrial region RNR1 IQR Interquartile range PM Particulate matter mtDNA Mitochondrial DNA 12S rRNA Mitochondrial ribosomal 12S rRNA D-loop Displacement loop Research Paper |
| Zdroj: | Epigenetics |
| ISSN: | 1559-2308 |
| Popis: | 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. The ENVIRONAGE birth cohort is supported by the EU Program "Ideas" (ERC-2012-StG 310898), by the Flemish Scientific Fund (FWO, N1516112/G.0.873.11.N.10), and Bijzonder Onderzoeks Fonds of Hasselt University (BOF). This work was also supported by funding from the National Institute of Environmental Health Sciences (R01ES021733, R01ES021357, and R21ES022694-01A1). |
| Databáze: | OpenAIRE |
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