Male gamete copies to characterize genome inheritance and generate progenies

Male factor infertility accounts for approximately 30% of infertility cases. When spermatozoa are extremely scarce, replicating the male gamete to fertilize a large cohort of oocytes is ideal. Additionally, patients with inherited disorders currently rely on pre-implantation genetic testing (PGT) to select healthy embryos, which raises ethical concerns owing to the generation of multiple embryos to select one healthy conceptus. Therefore, it would be beneficial to decode the genetics of a single sperm cell before conceptus generation. In this study, we demonstrated the feasibility of replicating the sperm genome via androgenesis and selecting the desired gamete before fertilization to preserve a specific paternal genotype, as confirmed by phenotypic observations and genetic testing in a murine model. We achieved satisfactory pre-implantation development rates with replicated male gametes and generated healthy offspring. Specifically, using 8-cell stage androgenetic embryos, a single spermatozoon can yield up to three conceptuses carrying an identical paternal haplotype.