Cited by 132Epigenetics and DNA MethylationBirth, Development, and HealthSmoking Behavior and Cessation

Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy

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Novakovic, Boris, Ryan, Joanne, Pereira, Natalie, Boughton, Berin, Craig, Jeffrey M, Saffery, Richard·2014·Epigenetics

Abstract

The intrauterine environment has the potential to "program" the developing fetus in a way that can be potentially deleterious to later health. While in utero environmental/stochastic factors are known to influence DNA methylation profile at birth, it has been difficult to assign specific examples of epigenetic variation to specific environmental exposures. Recently, several studies have linked exposure to smoking with DNA methylation change in the aryl hydrocarbon receptor repressor (AHRR) gene in blood. This includes hypomethylation of AHRR in neonatal blood in response to maternal smoking in pregnancy. The role of AHRR as a negative regulator of pathways involved in pleiotropic responses to environmental contaminants raises the possibility that smoking-induced hypomethylation is an adaptive response to an adverse in utero environmental exposure. However, the tissue specificity of the response to maternal smoking, and the stability of the methylation changes early in life remain to be determined. In this study we analyzed AHRR methylation in three cell types-cord blood mononuclear cells (CBMCs), buccal epithelium, and placenta tissue-from newborn twins of mothers who smoked throughout pregnancy and matched controls. Further, we explored the postnatal stability of this change at 18 months. Our results confirm the previous association between maternal smoking and AHRR methylation in neonatal blood. In addition, this study expands the region of AHRR methylation altered in response to maternal smoking during pregnancy and reveals the tissue-specific nature of epigenetic responses to environmental exposures in utero. Further, the evidence for postnatal stability of smoking-induced epigenetic change supports a role for epigenetics as a mediator of long-term effects of specific in utero exposures in humans. Longitudinal analysis of further specific exposures in larger cohorts is required to examine the extent of this phenomenon in humans.

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  • Novakovic and colleagues demonstrated persistent AHRR hypomethylation in blood monocytes at 1 year of age.

    “Novakovic and colleagues 76 recently demonstrated persistent AHRR hypomethylation in blood monocytes at 1 year of age, and a separate longitudinal study detected persistent changes at 7 years of age.72,77”

    From Impact of Tobacco Smoke and Nicotine Exposure on Lung Development (2016) · cites this paper as [76]

    The section “Maternal smoking-induced hypomethylation of AHRR is maintained at 18 mo” reports that the methylation difference associated with maternal smoking persisted after birth. It measured peripheral blood mononuclear cells at 18 months, not isolated monocytes at 1 year of age. (LLM, conf=0.88)

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  • These epigenetic changes in AHRR methylation persist well into postnatal life.

    “These epigenetic changes in AHRR methylation persist well into postnatal life.”

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Authors
Novakovic, B., Ryan, J., Pereira, N., Boughton, B., Craig, J. M., & Saffery, R.
Affiliations
  • Royal Children's Hospital (AU)
  • The University of Melbourne (AU)
Corresponding author
Novakovic, Boris
Venue
Epigenetics
Published
2013-11-22
Volume
9
Issue
3
Pages
377-386
ISSN
  • 1559-2294 (ISSN-L)
  • 1559-2308
OpenAlex
W2068396680
Cited by
131
References
36
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 11 · 2021: 3 · 2020: 9 · 2019: 11 · 2018: 10 · 2017: 25 · 2016: 16 · 2015: 19 · 2014: 8 · 2012: 1
FWCI
6.42
Type
journal article
Language
en
Open access
Locations
  • Epigenetics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Murdoch University Research Portal (submittedVersion)
Funders
  • State Government of Victoria
  • Medical Research Council
  • National Health and Medical Research Council (437015, 607358)
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 › Physiology › Smoking Behavior and Cessation
Keywords
AHRR, DNA methylation, maternal smoking, prenatal exposure, epigenetic programming, cord blood mononuclear cells, buccal epithelium, placenta, tissue specificity, neonatal blood, environmental pollutants, fetal development
MeSH terms
Female, Fetal Blood, Humans, Infant, Newborn, Maternal-Fetal Exchange, Organ Specificity, Pregnancy, Prenatal Exposure Delayed Effects, Repressor Proteins, Smoking, Case-Control Studies, Maternal Exposure, DNA Methylation, Epigenesis, Genetic, Basic Helix-Loop-Helix Proteins

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