Maternal smoking during pregnancy is associated with mitochondrial DNA methylation

• Type of Material: Article
• Authors: David A. Armstrong, Dartmouth-Hitchcock Medical Center; Benjamin B. Green, Dartmouth-Hitchcock Medical Center; Bailey A Blair, Dartmouth-Hitchcock Medical Center; Dylan J. Guerin, Dartmouth-Hitchcock Medical Center; Julia F. Litzky, Dartmouth-Hitchcock Medical Center; Niraj R. Chavan, University of Kentucky; Kevin J. Pearson, University of Kentucky; Carmen Marsit, Emory University
• Language: English
• Date: 2016-10-20
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Oxford University Press
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/eep/dvw020
• Title of Journal or Parent Work: Environmental Epigenetics
• ISSN: 2058-5888
• Volume: 2
• Issue: 3
• Start Page: dvw020
• End Page: dvw020
• Grant/Funding Information: This work was supported by the U.S. National Institutes of Health (NIH), National Institute of Mental Health (NIMH) R01MH094609, National Institutes for Environmental Health Sciences (NIEHS) R01ES022223, and P01 ES022832 and by the US Environmental Protectional Agency (EPA) grant RD83544201.
• Keywords: mitochondria; maternal smoking; DNA mthylation; placenta; pregnancy
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, Epidemiology; Health Sciences, Pharmacology

Abstract

Maternal smoking during pregnancy (MSDP) has detrimental effects on fetal development and on the health of the offspring into adulthood. Energy homeostasis through ATP production via the mitochondria (mt) plays a key role during pregnancy. This study aimed to determine if MSDP resulted in differences in DNA methylation to the placental mitochondrial chromosome at the transcription and replication control region, the D-Loop, and if these differences were also present in an alternate neonatal tissue (foreskin) in an independent birth cohort. We investigated mtDNA methylation by bisulfite-pyrosequencing in two sections of the D-Loop control region and in long interspersed nuclear element-1 (LINE-1) genomic sequences in placenta from 96 mother–newborn pairs that were enrolled in a Rhode Island birth cohort along with foreskin samples from 62 infants from a Kentucky birth cohort. In both placenta and foreskin, mtDNA methylation in the light chain D-Loop region 1 was positively associated with MSDP in placenta (difference+2.73%) (P=0.001) and foreskin (difference+1.22%) (P=0.08). Additionally, in foreskin, a second segment of the D-Loop-heavy chain region 1 showed a small but significant change in methylation with MSDP (+0.4%, P=0.04). No methylation changes were noted in either tissue at the LINE-1 repetitive element. We identified a similar pattern of epigenetic effect to mitochondria arising in cells from different primordial lineages and in different populations, associated with MSDP. These robust and consistent results build evidence that MSDP may impact mt D-Loop methylation, as one mechanism through which this exposure affects newborn health.