Maternal smoking during pregnancy is associated with mitochondrial DNA methylation
Open accessAbstract
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.
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Factors including traffic-related elemental carbon, maternal smoking, endogenous metabolites, cell senescence, and ageing alter mtDNA methylation.
“Furthermore, mtDNA methylation is disturbed by environmental and other factors, such as traffic-derived elemental carbon105, maternal smoking106, endogenous metabolites107, cell senescence108 and ageing109.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [106]
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- Authors
- Armstrong, D. A., Green, B. B., Blair, B. A., Guerin, D. J., Litzky, J. F., Chavan, N. R., Pearson, K. J., & Marsit, C. J.
- Affiliations
- Dartmouth–Hitchcock Medical Center (US)
- University of Kentucky HealthCare (US)
- Dartmouth College (US)
- Corresponding author
- Marsit, Carmen J.
- ORCID
- Venue
- Environmental Epigenetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08
- Volume
- 2
- Issue
- 3
- Pages
- dvw020
- ISSN
- 1674-5507 (ISSN-L)
- 2058-5888
- PMC
- PMC5624552
- OpenAlex
- W2536044826
- Cited by
- 36
- References
- 52
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 2
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- Current Zoology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- U.S. Environmental Protection Agency (P01ES022832, R01MH094609, R01ES022223, RD83544201)
- National Institutes of Health (RD83544201)
- National Institute of Mental Health (R01MH094609, RD83544201)
- National Institute of Environmental Health Sciences (P01ES022832, R01ES022223, ES022832, RD 83544201)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- smoking during pregnancy, mitochondrial DNA methylation, placenta, neonatal foreskin, D-loop, LINE-1, epigenetics, fetal development, newborn health, energy homeostasis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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