Paternal preconception exercise and sperm epigenetic mechanisms: a systematic review on offspring health.

INTRODUCTION

Paternal biology before conception can influence offspring health beyond DNA sequence inheritance. Paternal exercise is a modifiable exposure that can remodel the male germline epigenome through DNA methylation, histone modifications, and small non-coding RNAs, potentially affecting offspring development and metabolism.

METHODS

This systematic review searched PubMed/MEDLINE, Scopus, Web of Science, LILACS, and EMBASE without year restrictions. Experimental animal studies were eligible if sires exercised before conception and reported sperm or offspring epigenetic outcomes alongside molecular or phenotypic measures. Study selection followed predefined criteria.

RESULTS

Of 14,409 records identified, 7836 duplicates were removed, and 6573 records were screened. Six studies met the inclusion criteria. Across treadmill and voluntary running paradigms, paternal exercise was associated with reduced offspring hippocampal DNA methylation, altered sperm small RNAs, decreased sperm H3K9 dimethylation, lower placental inflammatory mRNA expression, and improved offspring outcomes, including spatial learning, anxiety-like behavior, endurance, mitochondrial respiration, glucose tolerance, and insulin sensitivity.

CONCLUSION

Paternal exercise before conception remodels the male germline and is associated with beneficial metabolic, mitochondrial, and behavioral adaptations in offspring through epigenetic mechanisms, supporting its potential relevance for intergenerational health.

PROTOCOL REGISTRATION: https://www.crd.york.ac.uk/prospero identifier is CRD420251141579.