Male gamete copies to characterize genome inheritance and generate progenies

Male factor infertility accounts for approximately 30% of infertile couples. When spermatozoa are extremely scarce, replicating the male gamete to fertilize a large cohort of oocytes would be ideal. Additionally, patients with inherited disorders currently rely on pre-implantation genetic diagnosis (PGD) to select healthy embryos, which raises ethical concerns due 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, confirmed by phenotypic observation and genetic testing, in a murine model. We achieved satisfactory pre-implantation developmental rates with replicated male gametes and were able to generate healthy offspring. Specifically, using 8-cell stage androgenetic embryos, a single spermatozoon can yield up to three conceptuses carrying the identical paternal haplotype.