Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy
Open accessAbstract
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)
Experimental — accuracy not yet measuredThese epigenetic changes in AHRR methylation persist well into postnatal life.
“These epigenetic changes in AHRR methylation persist well into postnatal life.”
From Impact of Tobacco Smoke and Nicotine Exposure on Lung Development (2016) · cites this paper as [76]
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Disrupted methylation patterns at birth persist in early childhood: a prospective cohort analysis
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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
- Publisher
- Informa UK Limited
- Published
- 2013-11-22
- Volume
- 9
- Issue
- 3
- Pages
- 377-386
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC4053456
- 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
- bronze
- doi.org
- 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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