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

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.