Title : Paternal Epigenetic Inheritance: A man’s exposome may impact health of his unborn children and grandchildren
Abstract:
The continuous exposure to air pollution and the growing number of manmade chemicals is a threat to biota and human health. These exposures can, together with other stressors, cause adverse effects, either alone or via complex interactions. The exposome can be defined as an individual’s cumulative lifetime environmental exposure and related biological responses. Our response to current exposures and disease vulnerability, is influenced by genetics, epigenetics, physiology, and health status, which involve alterations in biological pathways induced by earlier exposures. It might even be influenced by your parents or grandparents’ exposures. At conception, the gametes deliver not only the genetic material to form an embryo, but also additional epigenetic information that could reflect the exposures and lifestyle behaviors of both parents. The alarming decrease in sperm counts and research indicating possible paternal transmission of phenotype through epigenetic mechanisms show that research on risk factors and implications are urgently needed. We aim to integrate experimental model systems, computational and omics tools, and epidemiological research to increase the understanding of if, and how, environmental exposures may affect male reproductive health and their children via paternal epigenetic inheritance. We recently published the first study of paternal transgenerational inheritance in frogs. This unique experiment took over 3 years to complete, from the exposure of male frogs (F0) to environmental concentrations of the pesticide linuron, until the grand-offspring (F2) was mated. Interestingly, the adult male offspring (F1) of linuron exposed fathers were smaller, demonstrated impaired spermatogenesis and reduced fertility, and additional evidence of endocrine system disruption. Impacts were further propagated to the F2 generation, providing evidence of transgenerational effects in amphibians. The adult F2 males showed increased weight and metabolic impairments, as well as less germ cell nests in testis. Our findings support a causal and complex role of pollutants in the occurring amphibian extinction. The results also provide important cross-species evidence of paternal epigenetic inheritance. We have similar unpublished data from other animal models indicating that chemical contaminants have the potential to induce alterations in sperm biomolecules that are transferred to the next generation during fertilization/embryogenesis, thereby affecting phenotype of the offspring via epigenetic mechanisms. To study this further, we are establishing a birth cohort, where we collect lifestyle data and biological samples from both mother and father, determine exposure to environmental chemicals—i.e. the chemical exposome—by comprehensive mass spectrometry workflows, and conduct detailed studies of sperm and paternal impact on child development/health. This cohort study is a long-term commitment to increase understanding and awareness of how the exposome may affect male reproductive health and child health through epigenetic inheritance.
