When Redox Balance Meets the Epigenome: The Redox–Epigenetic Interface in Spermatogenesis and Beyond

Reactive oxygen species (ROS) modulate physiological signaling throughout spermatogenesis, but disruption of redox homeostasis by environmental exposures and paternal lifestyle factors can lead to oxidative stress. Although its effects on sperm DNA integrity and function have been extensively studied, how oxidative stress intersects with epigenetic regulation in the male germline remains less fully integrated. This review examines the redox–epigenetic interface across spermatogenesis, focusing on DNA methylation, histone post-translational modifications, and chromatin remodeling. We discuss interconnected mechanisms through which redox perturbations may influence the germline epigenome, including changes in cellular metabolism and the availability of cofactors required for epigenetic reactions, modulation of DNA- and histone-modifying enzymes, and oxidative modifications of DNA and chromatin-associated proteins. These interactions are considered in the developmental context of spermatogonial differentiation, meiosis, and spermiogenesis, when the molecular processes governing epigenetic regulation and sperm chromatin organization differ substantially. We further examine how redox-associated alterations in DNA methylation and chromatin features may persist in mature sperm and contribute to the paternal molecular information delivered at fertilization. Understanding the redox–epigenetic interface is essential to clarify how environmental and metabolic exposures may reshape the male germline epigenome and influence the paternal molecular contribution to early embryonic development.