Adverse health effects and stresses on offspring due to paternal exposure to harmful substances

Recent epidemiological investigations report that environmental factors, such as exposure to harmful substances and stress related to unhealthy lifestyles, can result in health risks to organisms. The involvement of paternal exposure to chemicals and stresses, which leads to a negative impact on physiological responses and developmental processes in descendants, has drawn scientific attention. In this comprehensive review, we systematically describe different exposure sources of intergenerational and transgenerational health effects, including smoking, atmospheric fine particulate matter, alcohol, obesogenic diet and chemical toxicants, as well as stress related to unhealthy lifestyles, such as early stress and trauma during early development. Furthermore, effects on paternal lineages through epigenetic mechanisms mediated by germ cells, including effects on reproduction, oxidative stress, nervous and immune systems, were reviewed. Collectively, these effects can affect genetic materials through DNA methylation, small noncoding RNAs and histone modifications in later generations. Specifically, neurotoxicity or brain development caused by paternal inheritance was reviewed for this research. To better understand the epigenetic mechanisms of phenotypic changes and pathological lesions, further studies should emphasize research on the effects on third or fourth generation (i.e., F₃ or F₄) of offspring, rather than only the first or second generation (i.e., F₁ or F₂), which is generally done. In particular, how the toxic effects of new pollutants on paternal heritage are transmitted to successive generations (i.e., F₃ and onward) should be more fully explored, and attempts should be made to find ways to alleviate the effects of the exposures on offspring.