Allogeneic germline stem cell transplantation restores fertility in nonablated recipient mice†

Spermatogonial stem cells (SSCs) colonize nonablated recipient testes. Autotransplantation of SSCs is expected to restore fertility in boys who become infertile due to cancer therapy. However, since the number of SSCs recovered from testis biopsies is small, increasing SSC number is a prerequisite. Additionally, residual spermatogenesis in the recipient testes may hinder colonization. Here, we evaluated the effects of SSC culture and endogenous spermatogenesis in syngeneic and allogeneic recipient mouse testes. While cultured SSCs colonized chemically-castrated mature testes, they showed limited colonization in nonablated testes. However, successful colonization occurred in immature nonablated testes. Although cultured SSCs from DBA/2 mice failed to colonize mature C57BL/6 testes, they colonized immature C57BL/6 testes without immunoconditioning. Offspring were produced via microinsemination using DBA/2 sperm or elongated spermatids generated in C57BL/6 testis. Therefore, the recipient's age is crucial for SSC autotransplantation, and our results also underscore dramatic changes in the immunological environment during testis maturation.