Spermatogonial Stem Cell Transplantation into Rhesus Testes Regenerates Spermatogenesis Producing Functional Sperm

SummarySpermatogonial stem cells (SSCs) maintain spermatogenesis throughout a man’s life and may have application for treating some cases of male infertility, including those caused by chemotherapy before puberty. We performed autologous and allogeneic SSC transplantations into the testes of 18 adult and 5 prepubertal recipient macaques that were rendered infertile with alkylating chemotherapy. After autologous transplant, the donor genotype from lentivirus-marked SSCs was evident in the ejaculated sperm of 9/12 adult and 3/5 prepubertal recipients after they reached maturity. Allogeneic transplant led to donor-recipient chimerism in sperm from 2/6 adult recipients. Ejaculated sperm from one recipient transplanted with allogeneic donor SSCs were injected into 85 rhesus oocytes via intracytoplasmic sperm injection. Eighty-one oocytes were fertilized, producing embryos ranging from four-cell to blastocyst with donor paternal origin confirmed in 7/81 embryos. This demonstration of functional donor spermatogenesis following SSC transplantation in primates is an important milestone for informed clinical translation.

Graphical AbstractFigure optionsDownload high-quality image (268 K)Download as PowerPoint slideHighlights
► Primate SSCs can be transplanted by ultrasound-guided rete testis injection
► Autologous SSCs regenerate spermatogenesis in chemotherapy-treated primates
► Allogeneic primate SSCs regenerate spermatogenesis in unrelated recipients
► Donor SSC-derived sperm can fertilize oocytes and lead to early embryo development