Abstract
The spermatogonial transplantation technique was developed by Dr. Ralph Brinster in 1994. Transplanted spermatogonial stem cells (SSCs) produce germ cell colonies after microinjection into the seminiferous tubules of infertile mice. This technique provided the first functional assay for SSCs. Although it became possible to produce transgenic animals using this transplantation technique in 2001, the lack of SSC culture systems prevented efficient genetic manipulation. To overcome this problem, a long-term SSC culture technique was developed in 2003. Cultured SSCs, designated as germline stem cells, allow drug selection of transfected SSCs, and knockout mice were produced in 2006. Using these techniques, it is now possible to address basic biological questions of SSC biology. They also open up new possibilities for male germline manipulation. In this review, we will briefly summarize our findings on SSCs and discuss unresolved issues that remain to be addressed.
Highlights
The spermatogonial transplantation technique was developed by Dr Ralph Brinster in 1994
We found that GDNF activates the phosphatidylinositol 3-kinase-AKT pathway, and that overexpression of constitutively active AKT enables germline stem cells (GSCs) to proliferate under GDNFfree conditions, demonstrating that GDNF-mediated AKT pathway activation is critical for self-renewal (Lee et al, 2007; Oatley et al, 2007)
It is established that GDNF and FGF2 simultaneously activate both AKT and MAP2K1 pathways in somatic cells, we found that FGF2 activates the MAP2K1 pathway more strongly than GDNF in GSCs
Summary
It was difficult to analyze SSCs by biochemical and molecular approaches because of their small population size. GDNF or FGF2 in vitro (GDNF-cultured spermatogonia: G-SPG; FGF2cultured spermatogonia: F-SPG) These cells formed colonies on laminin-coated dish with distinct morphologies, both of them could maintain SSC activity and restore fertility of infertile mice by spermatogonial transplantation even after 4 months of culture, demonstrating that. We have not observed significant difference in colonization efficiency after long-term culture of both cell types These results revealed that GDNF is not the only self-renewal factor for SSCs. There are probably additional molecules involved in SSC selfrenewal, such as FGF8, CSF1, WNT3A, WNT5A, WNT6, and VEGFA (Oatley et al, 2009; Yeh et al, 2011, 2012; Lu et al, 2013; Hasegawa and Saga, 2014; Takase and Nusse, 2016; Tanaka et al, 2016). This is true when a transplantation assay is not employed in the analysis
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