Considerations for recipient male selection in a livestock Surrogate Sire breeding strategy

Surrogate Sires is a novel breeding technology for increasing the rate of genetic gain in food animal production settings through natural mating. As an overarching concept, a surrogate sire is a male possessing testes devoid of germ cells yet capable of harboring spermatogenesis following introduction of donor germline. The utility of this technology relies on recipient males that are not only germline ablated and capable of harboring donor-derived spermatogenesis but also otherwise phenotypically normal and readily produced. Since the advent of spermatogenic stem cell transplantation in mice, many methods have been used to generate surrogate males by either removing germline with cytotoxic treatments or preventing germ cell survival and/or development through gene editing. At present, the use of gene editing to cause germline ablation shows the most promise as the precise inactivation of genes involved in germ cell development allow for testis-specific effects and have been assessed for the ability to harbor spermatogenesis from introduced donor germline. Of particular interest is the knockout of NANOS2 as the consistent germline ablation phenotype and proven production of donor-derived spermatogenesis combined with the fertility of both knockout females and heterozygous males establishes a clear and simple means for the scaling and use of Surrogate Sires in livestock production.