Epigenetic dysregulation in idiopathic male infertility: The role of aberrant histone post-translational modifications

Idiopathic male infertility (IMI), a condition with no clear clinical reason, represents a growing proportion of male reproductive complications. Traditional semen analysis fails to identify underlying etiology, leaving no indication for the sperm epigenome, particularly histone post-translational modifications which is emerging as a highly sensitive indicator of reproductive outcomes. This review synthesises evidence that different environmental toxicants such as chemical exposure, oxidative stress and lifestyle habits induce epigenetic alterations by disrupting histone post-translational modifications (HPTMs) in sperm. We critically evaluate how toxicant-induced dysregulation of critical HPTMs, serves as a key mechanism contributing to compromised spermatogenesis, poor sperm quality, and adverse reproductive outcomes. We explore the mechanisms through which specific toxicants alter the enzymatic machinery governing HPTM equilibrium. This comprehensive review highlights the utility of HPTMs as sensitive biomarkers of reproductive toxicity and underlines the urgent need for further research into the epigenetic mechanisms targeted by environmental contaminants to better assess reproductive risk and therapeutic strategies.