Male germ cell technologies in large animals

The manipulation of male germ cells presents significant opportunities for introducing heritable genetic changes in large animal species. As the foundation of lifelong spermatogenesis, spermatogonial stem cells (SSC) provide a unique target for stable genetic modifications that can be passed to future generations and produce genetically modified offspring. Recent progress in gene editing and transplantation techniques has improved the value of germ cells as a platform for transgenerational genetic inheritance in large animals. Yet, substantial challenges remain, including the lack of robust SSC culture systems, species-specific differences, and technical difficulties for gene editing and SSC transplantation. Additional concerns, such as editing efficiency, off-target mutations, immune rejection, and regulatory acceptance, may further limit translation. This review summarizes the current state of male germ cell technologies in large animals, focusing on tools, methodologies, and applications. We also highlight critical limitations and ethical considerations and outline future directions of the field. Overall, germ cell technologies are positioned as a promising approach at the interface of reproductive biology, biotechnology, and translational science.