Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males

Significance Transfer of sperm-producing stem cells isolated from a donor male into testes of a recipient male has important applications for preserving germplasm and as a conduit for widespread dissemination of desirable genetics in livestock production. A key aspect is surrogate males that lack endogenous germline but are otherwise physiologically normal. Here we demonstrate that male mice, pigs, and goats rendered genetically sterile by CRISPR-Cas9 editing of the NANOS2 gene support donor-derived spermatogenesis following allogeneic stem cell transplantation. In addition, we show that CRISPR-Cas9 editing of the NANOS2 gene in cattle leads to male germline ablation. These findings represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals.