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Updated: Sep 20, 2025
Germ Cell Transplantation and Testis Tissue Xenografting in Mice
Published on: February 6, 2012
Xenotransplantation of Human Spermatogonia Into Various Mouse Recipient Models
Dongli Liang1, Qi Sun2, Zijue Zhu3
1Laboratory Animal Center, Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Spermatogonial stem cells are the foundation of continuous spermatogenesis in adult mammals. Xenograft models have been established to define human SSCs, mostly using infertile and immune-deficient mice as the recipients for human germ cell transplantation. However, it is time-consuming to prepare such recipients using irradiation or chemotherapeutic agents, and this approach may also introduce confounding factors when residual endogenous germ cells recover in transplanted recipients. It remains to be determined whether immune-competent genetically infertile mice can be suitable recipients for xenotransplantation. In this study, we observed similar engraftment efficiencies when using spermatogonia from human biopsied testes across immune-deficient nude mice, immune-competent ICR mice, and genetically infertile Kit mice, suggesting minimal immunological rejection from immune-competent mouse recipients upon xenotransplantation of human germ cells. More importantly, we derived EpCAM negative and TNAP positive spermatogonia-like cells (SLCs) from human pluripotent stem cells (PSCs), which highly expressed spermatogonial markers including PLZF, INTERGRINα6, TKTL1, CD90, and DRMT3. We found that upon transplantation, these SLCs proliferated and colonized at the basal membrane of seminiferous tubules in testes of both immune-deficient nude mice and Kit mice, though complete spermatogenesis would likely require supporting human signaling factors and microenvironment. Taken together, our study functionally defined the cell identity of PSC-derived SLCs, and supported xenotransplantation using genetically infertile recipients as a convenient model for functionally evaluating spermatogonia derived from different species.
Insights
Genetically infertile mice can serve as suitable recipients for human germ cell xenotransplantation, simplifying research. This study defines spermatogonia-like cells derived from pluripotent stem cells for potential use in these models.
Area of Science:
- Reproductive biology and stem cell research.
- Mammalian spermatogenesis and germ cell transplantation.
Background:
- Spermatogonial stem cells (SSCs) are crucial for continuous sperm production in adult mammals.
- Current human SSC xenotransplantation models often use immune-deficient mice, requiring time-consuming preparation and potentially introducing confounding factors.
- The suitability of immune-competent, genetically infertile mice as recipients for xenotransplantation remains largely undetermined.
Purpose of the Study:
- To evaluate the efficacy of using immune-competent, genetically infertile mice as recipients for human germ cell xenotransplantation.
- To functionally define spermatogonia-like cells (SLCs) derived from human pluripotent stem cells (PSCs).
- To assess the engraftment and colonization potential of PSC-derived SLCs in mouse testes.
Main Methods:
- Xenotransplantation of human spermatogonia from biopsied testes into immune-deficient nude mice, immune-competent ICR mice, and genetically infertile KitW/W-v mice.
- Derivation of EpCAM negative and TNAP positive SLCs from human PSCs.
- Analysis of SLC marker expression (PLZF, INTERGRINα6, TKTL1, CD90, DRMT3) and assessment of their colonization in recipient mouse testes.
Main Results:
- Similar engraftment efficiencies were observed for human spermatogonia across all tested mouse recipient types, indicating minimal immunological rejection in immune-competent mice.
- PSCs successfully generated SLCs expressing key spermatogonial markers.
- Transplanted SLCs proliferated and colonized the basal membrane of seminiferous tubules in both immune-deficient and genetically infertile mouse testes.
Conclusions:
- Genetically infertile mice are suitable and convenient recipients for human germ cell xenotransplantation, offering a simplified alternative to irradiation or chemotherapy-treated models.
- The study functionally characterized PSC-derived SLCs, confirming their identity as spermatogonia-like cells.
- Further research is needed to optimize complete spermatogenesis, potentially by incorporating human signaling factors and microenvironment cues.
