Characterization, Cryopreservation, and Ablation of Spermatogonial Stem Cells in Adult Rhesus Macaques

Spermatogonial stem cells (SSCs) are at the foundation of mammalian spermatogenesis. Whereas rare Asingle spermatogonia comprise the rodent SSC pool, primate spermatogenesis arises from more abundant Adark and Apale spermatogonia, and the identity of the stem cell is subject to debate. The fundament...

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Bibliographic Details
Published in:	Stem cells (Dayton, Ohio) Vol. 25; no. 9; pp. 2330 - 2338
Main Authors:	Hermann, Brian P., Sukhwani, Meena, Lin, Chih‐Cheng, Sheng, Yi, Tomko, Jamie, Rodriguez, Mario, Shuttleworth, Jennifer J., McFarland, David, Hobbs, Robin M., Pandolfi, Pier Paolo, Schatten, Gerald P., Orwig, Kyle E.
Format:	Journal Article
Language:	English
Published:	Bristol John Wiley & Sons, Ltd 01-09-2007
Subjects:	Animals Antineoplastic Agents, Alkylating - adverse effects Antineoplastic Agents, Alkylating - pharmacology Busulfan Busulfan - adverse effects Busulfan - pharmacology Chemotherapy Cryopreservation Dose-Response Relationship, Drug Infertility Infertility, Male - chemically induced Macaca mulatta Male Mice Mice, Nude Models, Biological Semen Preservation - adverse effects Sperm Count Spermatogenesis Spermatogenesis - drug effects Spermatogonia - cytology Spermatogonia - drug effects Spermatogonia - transplantation Spermatogonial stem cells Stem Cell Transplantation Stem Cells - cytology Testis - anatomy & histology Testis - drug effects Transplantation, Heterologous Xenotransplantation
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Summary:	Spermatogonial stem cells (SSCs) are at the foundation of mammalian spermatogenesis. Whereas rare Asingle spermatogonia comprise the rodent SSC pool, primate spermatogenesis arises from more abundant Adark and Apale spermatogonia, and the identity of the stem cell is subject to debate. The fundamental differences between these models highlight the need to investigate the biology of primate SSCs, which have greater relevance to human physiology. The alkylating chemotherapeutic agent, busulfan, ablates spermatogenesis in rodents and causes infertility in humans. We treated adult rhesus macaques with busulfan to gain insights about its effects on SSCs and spermatogenesis. Busulfan treatment caused acute declines in testis volume and sperm counts, indicating a disruption of spermatogenesis. One year following high‐dose busulfan treatment, sperm counts remained undetectable, and testes were depleted of germ cells. Similar to rodents, rhesus spermatogonia expressed markers of germ cells (VASA, DAZL) and stem/progenitor spermatogonia (PLZF and GFRα1), and cells expressing these markers were depleted following high‐dose busulfan treatment. Furthermore, fresh or cryopreserved germ cells from normal rhesus testes produced colonies of spermatogonia, which persisted as chains on the basement membrane of mouse seminiferous tubules in the primate to nude mouse xenotransplant assay. In contrast, testis cells from animals that received high‐dose busulfan produced no colonies. These studies provide basic information about rhesus SSC activity and the impact of busulfan on the stem cell pool. In addition, the germ cell‐depleted testis model will enable autologous/homologous transplantation to study stem cell/niche interactions in nonhuman primate testes. Disclosure of potential conflicts of interest is found at the end of this article.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1066-5099 1549-4918
DOI:	10.1634/stemcells.2007-0143