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Title: | Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIRONAGE birth cohort study | Authors: | JANSSEN, Bram Byun, Hyang-Min GYSELAERS, Wilfried Lefebvre, Wouter Baccarelli, Andrea A. NAWROT, Tim |
Issue Date: | 2015 | Publisher: | TAYLOR & FRANCIS INC | Source: | Epigenetics, 10 (6), p. 536-544 | Abstract: | 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. | Notes: | [Janssen, Bram G.; Nawrot, Tim S.] Hasselt Univ, Ctr Environm Sci, Diepenbeek, Belgium. [Byun, Hyang-Min; Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Lab Environm Epigenet, Boston, MA 02115 USA. [Gyselaers, Wilfried] East Limburg Hosp, Dept Obstet, Genk, Belgium. [Gyselaers, Wilfried] Hasselt Univ, Dept Physiol, Diepenbeek, Belgium. [Lefebvre, Wouter] Flemish Inst Technol Res VITO, Mol, Belgium. [Nawrot, Tim S.] Leuven Univ KU Leuven, Dept Publ Hlth Occupat Environm & Insurance Med, Leuven, Belgium. | Keywords: | air pollution; DNA methylation; epigenetics; mitochondria; mitochondrial DNA content; mitochondrial DNA methylation; particulate matter; placenta;particulate matter; mitochondrial DNA methylation; epigenetics; mitochondria; placenta; mitochondrial DNA content; DNA methylation; air pollution; 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 | Document URI: | http://hdl.handle.net/1942/19003 | ISSN: | 1559-2294 | e-ISSN: | 1559-2308 | DOI: | 10.1080/15592294.2015.1048412 | ISI #: | 000355682500010 | Rights: | © Bram G Janssen, Hyang-Min Byun, Wilfried Gyselaers, Wouter Lefebvre, Andrea A Baccarelli, and Tim S Nawrot. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.o rg/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2016 |
Appears in Collections: | Research publications |
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