The impact of exercise on sperm epigenetic modification and intergenerational inheritance.

Abstract

Paternal environmental factors can influence offspring health intergenerationally through alterations in sperm epigenetics. Exercise, as a key modifiable lifestyle factor, may similarly affect epigenetic inheritance. Emerging evidence from animal and human studies indicates that exercise modulates sperm DNA methylation and noncoding RNA expression. In animal models, paternal exercise has also been linked to changes in offspring phenotypes. However, inconsistencies exist across studies because of variations in exercise modalities and the specific epigenetic markers analyzed. More importantly, the mechanisms underlying the relationship between sperm epigenetic alterations and offspring phenotypes remain unclear. This review integrates evidence from January 2010 to December 2025 to summarize exercise-induced changes in sperm epigenetics and their associations with offspring metabolic and behavioral outcomes. It critically discusses major inconsistencies in the current literature and highlights underexplored areas, including exercise-induced changes in histone modifications and chromatin architecture in sperm, as well as a striking lack of human data on offspring health. We propose that future rigorous exercise standardization, multidimensional epigenetic profiling, well-designed human studies, and functional validation are essential to establish causality and translate findings into effective interventional strategies.