Mitochondrial DNA methylation in placental tissue: a proof of concept study by means of prenatal environmental stressors
| Autor: | Hyang-Min Byun, Tim S. Nawrot, Dries S. Martens, Bram G. Janssen, Stijn Vos |
|---|---|
| Přispěvatelé: | VOS, Stijn, NAWROT, Tim, MARTENS, Dries, Hyang-Min Byun, JANSSEN, Bram |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research air pollution markers Mitochondrion DISEASE 0302 clinical medicine Pregnancy Genetics & Heredity PARTICULATE AIR-POLLUTION mtDNA Brief Report DOHaD NON-CPG METHYLATION Methylation Mitochondria medicine.anatomical_structure birthweight Maternal Exposure 030220 oncology & carcinogenesis DNA methylation Birth Cohort Female HEALTH Life Sciences & Biomedicine Biochemistry & Molecular Biology Mitochondrial DNA prenatal placenta Birth weight Biology DNA Mitochondrial Proof of Concept Study smoking Andrology 03 medical and health sciences Placenta medicine Humans EXPOSURE Molecular Biology Science & Technology DNA Methylation medicine.disease BIRTH-WEIGHT 030104 developmental biology CHAIN Pyrosequencing Particulate Matter methylation |
| Zdroj: | Epigenetics article-version (VoR) Version of Record |
| ISSN: | 1559-2308 1559-2294 |
| DOI: | 10.1080/15592294.2020.1790923 |
| Popis: | While previous studies have demonstrated that prenatal exposure to environmental stressors is associated with mitochondrial DNA (mtDNA) methylation, more recent investigations are questioning the accuracy of the methylation assessment and its biological relevance. In this study, we investigated placental mtDNA methylation while accounting for methodological issues such as nuclear contamination, bisulphite conversion, and PCR bias. From the ENVIRONAGE birth cohort, we selected three groups of participants (n = 20/group). One group with mothers who smoked during pregnancy (average 13.2 cig/day), one group with high air pollutant exposure (PM2.5: 16.0 +/- 1.4 mu g/m(3), black carbon: 1.8 +/- 0.3 mu g/m(3)) and one control group (non-smokers, PM2.5: 10.6 +/- 1.7 mu g/m(3), black carbon: 0.9 +/- 0.1 mu g/m(3)) with low air pollutant exposure. DNA methylation levels were quantified in two regions of the displacement loop control region (D-loopandLDLR2) by bisulphite pyrosequencing. Additionally, we measured DNA methylation on nuclear genes involved in mitochondrial maintenance (PINK1, DNA2, andPOLG1) and assessed mtDNA content using qPCR. AbsoluteD-loopmethylation levels were higher for mothers that smoked extensively (+0.36%, 95% CI: 0.06% to 0.66%), and for mothers that were highly exposed to air pollutants (+0.47%, 95% CI: 0.20% to 0.73%). The relevance of our findings is further supported, asD-loopmethylation levels were correlated with placental mtDNA content (r = -0.40, p = 0.002) and associated with birth weight (-106.98 g, 95% CI: -209.60 g to -4.36 g for an IQR increase inD-loopmethylation). Most notably, our data demonstrates relevant levels of mtDNA methylation in placenta tissue, with significant associations between prenatal exposure to environmental stressors andD-loopmethylation. This work was supported by the Research Foundation Flanders [G082317N]; Research Foundation Flanders [N1518119]. Janssen, BG (corresponding author), Hasselt Univ, Ctr Environm Sci, B-3590 Diepenbeek, Belgium. bram.janssen@uhasselt.be |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|