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15 April 2009 Spermatogonial Stem Cells Derived from Infertile Wv/Wv Mice Self-Renew In Vitro and Generate Progeny Following Transplantation
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Abstract

Loss-of-function mutation of the Kit gene causes a severe defect in spermatogenesis that results in infertility due to the inability of its cognate ligand, KIT ligand (KITL), to stimulate spermatogonial proliferation and differentiation. Although self-renewal of mouse spermatogonial stem cells (SSCs) depends on glial cell line-derived neurotrophic factor (GDNF), there is no unequivocal evidence that SSCs with a KIT deficiency can self-renew in vivo or in vitro. In the testis of Wv/Wv mice, in which the KIT tyrosine kinase activity is impaired, spermatogonia with SSC phenotype were identified. When Wv/Wv spermatogonia were cultured in an SSC culture system supplemented with GDNF in a 10% O2 atmosphere, they formed clumps and proliferated continuously. An atmosphere of 10% O2 was better than 21% O2 to support SSC self-renewal. When Wv/Wv clump-forming germ cells were transplanted into testes of infertile wild-type busulfan-treated mice, they colonized the seminiferous tubules but did not differentiate. However, when transplanted into the testes of infertile W/Wv pups, they restored spermatogenesis and produced spermatozoa, and progeny were generated using microinsemination. These results clearly show that SSCs exist in Wv/Wv testes and that they proliferate in vitro similar to wild-type SSCs, indicating that a functional KIT protein is not required for SSC self-renewal. Furthermore, the results indicate that a defect of KIT/KITL signaling of Wv/Wv SSCs does not prevent spermatogonial differentiation and spermatogenesis in some recipient strains.

Hiroshi Kubota, Mary R. Avarbock, Jonathan A. Schmidt, and Ralph L. Brinster "Spermatogonial Stem Cells Derived from Infertile Wv/Wv Mice Self-Renew In Vitro and Generate Progeny Following Transplantation 1," Biology of Reproduction 81(2), (15 April 2009). https://doi.org/10.1095/biolreprod.109.075960
Received: 4 January 2009; Accepted: 1 March 2009; Published: 15 April 2009
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