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Title: | Regulating role of fetal thyroid hormones on placental mitochondrial DNA methylation: epidemiological evidence from the ENVIRONAGE birth cohort study | Authors: | JANSSEN, Bram Byun, Hyang-Min ROELS, Harry GYSELAERS, Wilfried PENDERS, Joris Baccarelli, Andrea A. NAWROT, Tim |
Issue Date: | 2017 | Publisher: | BIOMED CENTRAL LTD | Source: | CLINICAL EPIGENETICS, 9, p. 1-10 (Art N° 66) | Abstract: | Background: Fetal development largely depends on thyroid hormone availability and proper placental function with an important role played by placental mitochondria. The biological mechanisms by which thyroid hormones exert their effects on mitochondrial function are not well understood. We investigated the role of fetal thyroid hormones on placental mitochondrial DNA (mtDNA) content and mtDNA methylation. We collected placental tissue and cord blood from 305 mother-child pairs that were enrolled between February 2010 and June 2014 in the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort (province of Limburg, Belgium). Placental mtDNA content was determined by qPCR and placental mtDNA methylation by bisulfite-pyrosequencing in two regions, i.e., the D-loop control region and 12S ribosomal RNA (MT-RNR1). The levels of free thyroid hormones (FT3, FT4) and thyroid-stimulating hormone (TSH) were measured in cord blood. Results: Cord blood FT3 and FT4 were inversely associated with placental mtDNA methylation at the MT-RNR1 (p <= 0.01) and D-loop (p <= 0.05) regions, whereas a positive association was observed for both hormones with placental mtDNA content (p <= 0.04). Assuming causality, we estimated that MT-RNR1 and D-loop methylation mediated, respectively, 77% [indirect effect +14.61% (95% CI 2.64 to 27.98%, p = 0.01)] and 47% [indirect effect +8.60% (95% CI 1.23 to 16.50%, p = 0.02] of the positive association between FT3 and placental mtDNA content. Mediation models with FT4 gave similar results but the estimated effect proportions were smaller compared with those of FT3 (54% and 24%, respectively). Conclusions: We showed that epigenetic modification at specific loci of the mitochondrial genome could intervene with the thyroid-dependent regulation of mitochondrial DNA copy numbers. | Notes: | [Janssen, Bram G.; Roels, Harry A.; Nawrot, Tim S.] Hasselt Univ, Ctr Environm Sci, Agoralaan Bldg D, B-3590 Diepenbeek, Belgium. [Byun, Hyang-Min] Newcastle Univ, Human Nutr Res Ctr, Inst Cellular Med, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England. [Roels, Harry A.] Catholic Univ Louvain, Louvain Ctr Toxicol & Appl Pharmacol LTAP, Brussels, Belgium. [Gyselaers, Wilfried] East Limburg Hosp, Dept Obstet, B-3600 Genk, Belgium. [Gyselaers, Wilfried; Penders, Joris] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. [Penders, Joris] East Limburg Hosp, Lab Clin Biol, B-3600 Genk, Belgium. [Baccarelli, Andrea A.] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Nawrot, Tim S.] Leuven Univ, Dept Publ Hlth & Primary Care, Occupat & Environm Med, Leuven, Belgium. | Keywords: | DNA methylation; Epigenetics; Mitochondria; Mitochondrial DNA content; Placenta; Fetal thyroid hormones;DNA methylation; epigenetics; mitochondria; mitochondrial DNA content; placenta; fetal thyroid hormones | Document URI: | http://hdl.handle.net/1942/24425 | ISSN: | 1868-7075 | e-ISSN: | 1868-7083 | DOI: | 10.1186/s13148-017-0366-y | ISI #: | 000403968700001 | Rights: | © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2018 |
Appears in Collections: | Research publications |
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