Sperm epigenome as a marker of environmental exposure and lifestyle, at the origin of diseases inheritance.

Paternal exposure to environmental challenges plays a critical role in the offspring's future health and the transmission of acquired traits through generations. This review summarizes our current knowledge in the new field of epigenomic paternal transmission of health and disease. Epidemiological studies identified that paternal ageing or challenges (imbalanced diets, stress, toxicants, cigarette smoke, alcohol) increased the risk of offspring to develop diseases such as cancer, metabolic, cardiovascular, and neurological diseases. These data were confirmed and deepened in animal models of exposure to challenges including low-protein, low-folate, high-fat diets, exposure to chemicals such as pesticides and herbicides. Even though some toxicants have mutagenic effect on sperm DNA, changes in sperm epigenome seem to be a common thread between different types of challenges. Indeed, epigenetic changes (DNA methylation, chromatin remodeling, small non-coding RNA) in sperm are described as new mechanisms of intergenerational transmission as demonstrated for dioxin, for example. Those epimutations induce dysregulation in genes expression involved in key cellular pathways such as reactive oxygen species and genome stability regulation, in brain-derived neurotrophic factor, calcium and glucocorticoid signaling, and in lipid and glucose metabolism, leading to diseases in offspring. Finally, since each type of environmental challenges has its own signature by inducing epimutations at specific genomic loci, the sperm epigenome might be used as a biomarker in toxicological and risk assessments.