Paternal smoking as a cause for transgenerational damage in the offspring

Abstract

In 2013, the World Health Organization referred to tobacco smoking as an epidemic and a great threat to human health. Despite the obvious exposures from first- and secondhand smoking contributing to illnesses, an increased cancer risk, and death, there is a hidden risk to the next generation(s) from transgenerational mutations. In human populations, paternal preconceptional germ cell damage leading to genomic instability in offspring has always been difficult to evaluate as preconceptional and gestational exposures usually cannot be analyzed independently. Clear indications have been found that the effect of pre- and periconceptional paternal smoking may have been transmitted to the offspring via the spermatozoal genome and epigenome. Hence, cigarette smoke has to be considered a human germ cell mutagen due to its potential of inducing transgenerational DNA alterations in the unexposed F1 offspring of smoking-exposed fathers. For cohort studies, the practice of almost exclusively employing mother–childbirth pairs for the evaluation of lifestyle factors, such as smoking, while excluding the fathers’ contribution has to be reconsidered. Evidence now strongly points to the necessity of including the fathers in order not to miss paternal transgenerational damage in the offspring. This applies for genetic, epigenetic, and other transmissible effects.