DNA methylation clock in bull sperm cells reveals the epigenetic aging characteristics and impact on fertility

BACKGROUND: Aging is a crucial factor influencing semen quality and fertility in bulls, with potential implications for reproductive management and genetic improvement programs. Understanding the molecular mechanisms underlying sperm cell aging is essential for assessing reproductive potential and improving livestock productivity. RESULTS: In this study, we developed an epigenetic clock for bull sperm cells using whole-genome bisulfite sequencing (WGBS) and reduced representation bisulfite sequencing (RRBS) on samples from Holstein stud bulls of different ages. Our analysis identified age-specific CpG sites and revealed distinct DNA methylation patterns associated with different age stages. The developed epigenetic clock demonstrated high accuracy in predicting the biological age of bull sperm cells, with significant correlations between epigenetic age acceleration (EAA) and semen quality traits such as fresh semen motility, frozen semen abnormality rate, and testicular circumference. Furthermore, we explored the involvement of transmembrane transport and other pathways in sperm cell aging, providing insights into the molecular mechanisms underlying semen quality changes. The study also established a cross-species human-bull sperm cell epigenetic clock, highlighting the potential for comparative studies on paternal biological aging. CONCLUSIONS: Our findings highlight the important role of DNA methylation regulation in sperm cell aging, providing a novel tool to evaluate reproductive potential in livestock. The creation of the bull sperm cell DNA methylation clock and the discovery of key molecular pathways linked to aging enhance our comprehension of sperm cell biology and provide insight into reproductive management and extending production longevity in cattle.