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Significance Glial cell line-derived neurotrophic factor (GDNF) growth factor induces spermatogonial stem cells to proliferate in culture to produce progenitor spermatogonia. Sertoli cell GDNF was thought responsible for this in the testis. We showed that testosterone triggers GDNF secretion by peritubular myoid (PM) cells in culture and that undifferentiated spermatogonia (spermatogonial stem cells and progenitors) co-cultured with testosterone-treated PM cells and transplanted to sterile mice restored spermatogenesis. To determine if PM cell GDNF is essential to maintain the undifferentiated spermatogonial population, we made mice lacking theGdnf gene in PM cells. The number of undifferentiated spermatogonia was severely depleted in 2-wk-old mice and adults were infertile. This is the first study, to our knowledge, to show that the undifferentiated spermatogonial pool cannot be maintained without GDNF from PM cells.

Targeting the Gdnf Gene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development