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Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review)

  • Authors:
    • Maria Vlachou
    • Giannoula Kyrkou
    • Vasiliki Epameinondas Georgakopoulou
    • Anastasia Kapetanaki
    • Victoria Vivilaki
    • Demetrios A. Spandidos
    • Athina Diamanti
  • View Affiliations / Copyright

    Affiliations: Department of Midwifery, School of Health and Care Sciences, University of West Attica, 12243 Athens, Greece, Department of Pathophysiology, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece, Neonatal Intensive Care Unit, Helena Venizelou General and Maternity Hospital, 11521 Athens, Greece, Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece
    Copyright: © Vlachou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 146
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    Published online on: June 23, 2025
       https://doi.org/10.3892/br.2025.2024
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Abstract

Tobacco use continues to pose a significant public health challenge, not only due to its immediate toxic effects but also because of its long‑lasting epigenetic consequences. The present review explores the complex and evolving field of epigenetics to examine how maternal, paternal and even grandparental smoking can alter the heritable regulation of gene expression, with consequences that span multiple generations. The focus is placed on DNA methylation as a central mechanism mediating these effects, particularly in the placenta and germ cells. Evidence from human cohort studies and animal models highlights that in utero exposure to cigarette smoke results in epigenetic reprogramming of fetal tissues, which can influence susceptibility to metabolic, respiratory and neurodevelopmental disorders throughout life. Moreover, paternal smoking, even before conception, has been linked to changes in sperm epigenetic markers, which may be transmitted to the offspring and disrupt developmental processes. These effects are not limited to the directly exposed generation; transgenerational inheritance of epigenetic marks has been documented, with grandmaternal smoking increasing the risk of asthma and reduced lung function in grandchildren. The review also discusses emerging strategies to mitigate these effects, such as maternal supplementation with folate and antioxidants, smoking cessation campaigns targeting prospective parents and public health policies informed by epigenetic science. The findings underscore the need to view tobacco exposure not merely as a personal behavior but as a modifiable risk factor with marked biological implications across generations. Understanding the epigenetic mechanisms underlying these outcomes is critical for shaping prevention strategies, guiding public health policy and informing ethical discourse on intergenerational health responsibility.
View Figures

Figure 1

DNA methylation patterns in the
placenta: Epigenetic regulation of gene expression and
developmental consequences. This figure illustrates the molecular
process of DNA methylation in placental tissue, highlighting the
role of DNMTs in the addition of methyl groups (CH3) to
CpG sites within the DNA sequence. These methylation events,
influenced by environmental factors such as maternal smoking,
regulate gene expression profiles critical for placental function.
Aberrant CpG methylation can lead to altered transcriptional
activity, potentially disrupting placental development and fetal
growth. The diagram emphasizes the mechanistic link between
epigenetic modifications and pregnancy outcomes, serving as a model
for how intrauterine environmental exposures can reprogram fetal
physiology via the placenta. DNMT, DNA methyltransferase.

Figure 2

Transgenerational epigenetic impact
of parental smoking on offspring gene expression. Parental smoking
during pregnancy or prior to conception can lead to epigenetic
alterations in germ cells or the developing fetus through
mechanisms such as DNA methylation and histone modifications. These
changes influence gene expression profiles, potentially resulting
in altered mRNA transcription. Such epigenetic marks may persist
beyond the exposed generation, contributing to disease
susceptibility and developmental alterations in subsequent
generations.
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Vlachou M, Kyrkou G, Georgakopoulou VE, Kapetanaki A, Vivilaki V, Spandidos DA and Diamanti A: Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review). Biomed Rep 23: 146, 2025.
APA
Vlachou, M., Kyrkou, G., Georgakopoulou, V.E., Kapetanaki, A., Vivilaki, V., Spandidos, D.A., & Diamanti, A. (2025). Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review). Biomedical Reports, 23, 146. https://doi.org/10.3892/br.2025.2024
MLA
Vlachou, M., Kyrkou, G., Georgakopoulou, V. E., Kapetanaki, A., Vivilaki, V., Spandidos, D. A., Diamanti, A."Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review)". Biomedical Reports 23.3 (2025): 146.
Chicago
Vlachou, M., Kyrkou, G., Georgakopoulou, V. E., Kapetanaki, A., Vivilaki, V., Spandidos, D. A., Diamanti, A."Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review)". Biomedical Reports 23, no. 3 (2025): 146. https://doi.org/10.3892/br.2025.2024
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Spandidos Publications style
Vlachou M, Kyrkou G, Georgakopoulou VE, Kapetanaki A, Vivilaki V, Spandidos DA and Diamanti A: Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review). Biomed Rep 23: 146, 2025.
APA
Vlachou, M., Kyrkou, G., Georgakopoulou, V.E., Kapetanaki, A., Vivilaki, V., Spandidos, D.A., & Diamanti, A. (2025). Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review). Biomedical Reports, 23, 146. https://doi.org/10.3892/br.2025.2024
MLA
Vlachou, M., Kyrkou, G., Georgakopoulou, V. E., Kapetanaki, A., Vivilaki, V., Spandidos, D. A., Diamanti, A."Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review)". Biomedical Reports 23.3 (2025): 146.
Chicago
Vlachou, M., Kyrkou, G., Georgakopoulou, V. E., Kapetanaki, A., Vivilaki, V., Spandidos, D. A., Diamanti, A."Smoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review)". Biomedical Reports 23, no. 3 (2025): 146. https://doi.org/10.3892/br.2025.2024
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