From fathers to futures: How the paternal exposome has an inter- and transgenerational influence on future offspring.

Abstract

The parental contribution to offspring health outcomes has long been considered solely genetic. A new hypothesis on the topic of Developmental origin of health and disease (DOHaD), focus on the paternal origin of health and disease (POHaD). An advantage of looking at paternal exposure is that exposure effects can only influence the gametes and do not influence the gestational conditions. POHaD studies the inter- and transgenerational effects of adverse exposures such as western diets, environmental pollutants, and alcohol consumption on the health outcomes of future offspring. This review tries to summarize the current understanding of inheritable epigenetic changes due to paternal exposures and the effects on the offspring, and current research strategies within POHaD. The status quo is that paternal exposure studies either study the effects of an exposure on the epigenome in gametes or the effects of an exposure on health outcomes in future offspring without connecting these dots comprehensively. To address this gap, POHaD must integrate studies looking for both exposures and interventions to prevent adverse health outcomes, instead of only identifying more exposures that cause adverse health outcomes. Therefore, the studies should focus on the three steps of inter- and transgenerational effects of paternal exposures. First, the paternal exposure; second, changes- and transmission of epigenetic markers; and last, changes in health outcomes. Insights in the three parts will help to identify adequate intervention methods in the form of planned abstinence of an exposure before conception, or counter-exposures such as exercise.