Abstract
Male infertility accounts for a substantial proportion of global infertility, yet its molecular basis remains incompletely defined. Emerging evidence implicates epigenetic dysregulation in impaired spermatogenesis and abnormal sperm function. We synthesize genomic, transcriptomic, and single-cell studies to clarify how DNA methylation, histone modifications, and noncoding RNAs contribute to oligoasthenozoospermia. We also appraise single-cell RNA sequencing, single-cell assay for transposase-accessible chromatin using sequencing, and integrative multi-omics for resolving cell-type and stage-specific regulation. These approaches resolve germ-cell lineages, map gene-regulatory networks, and link chromatin states with transcription across spermatogenesis. Finally, we discuss translational implications for diagnostics, biomarkers, and therapeutic strategies, including antioxidant regimens, varicocele management, and assisted reproductive technologies outcomes. In conclusion, integrating epigenetics with single-cell technologies has enhanced our understanding of male germ cell development and identified potential research directions to improve reproductive health.