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The study and manipulation of spermatogonial stem cells using animal models

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Abstract

Spermatogonial stem cells (SSCs) are a rare group of cells in the testis that undergo self-renewal and complex sequences of differentiation to initiate and sustain spermatogenesis, to ensure the continuity of sperm production throughout adulthood. The difficulty of unequivocal identification of SSCs and complexity of replicating their differentiation properties in vitro have prompted the introduction of novel in vivo models such as germ cell transplantation (GCT), testis tissue xenografting (TTX), and testis cell aggregate implantation (TCAI). Owing to these unique animal models, our ability to study and manipulate SSCs has dramatically increased, which complements the availability of other advanced assisted reproductive technologies and various genome editing tools. These animal models can advance our knowledge of SSCs, testis tissue morphogenesis and development, germ-somatic cell interactions, and mechanisms that control spermatogenesis. Equally important, these animal models can have a wide range of experimental and potential clinical applications in fertility preservation of prepubertal cancer patients, and genetic conservation of endangered species. Moreover, these models allow experimentations that are otherwise difficult or impossible to be performed directly in the target species. Examples include proof-of-principle manipulation of germ cells for correction of genetic disorders or investigation of potential toxicants or new drugs on human testis formation or function. The primary focus of this review is to highlight the importance, methodology, current and potential future applications, as well as limitations of using these novel animal models in the study and manipulation of male germline stem cells.

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Acknowledgments

We thank the current and former trainees in the lab for their contribution to the published work presented here. We also thank the animal care personnel at the Prairie Swine Centre, the Animal Care Unit of the Western College of Veterinary Medicine, and the Laboratory Animal Services Unit of the College of Medicine.

Funding

This study was supported by grants to A. Honaramooz from the Natural Sciences and Engineering Research Council (NSERC) of Canada, and the Saskatchewan Health Research Foundation (SHRF). Scholarships were provided to F. Ibtisham and A.H. Awang-Junaidi by the University of Saskatchewan’s Colleges of Graduate and Postdoctoral Studies, and Western College of Veterinary Medicine. Financial support was also provided to A. H. Awang-Junaidi by the Malaysian Ministry of Higher Education.

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  1. Awang Hazmi Awang-Junaidi

    Present address: Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Darul Ehsan, Malaysia

  2. Fahar Ibtisham and Awang Hazmi Awang-Junaidi contributed equally to this work.

Authors and Affiliations

  1. Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5B4, Canada

    Fahar Ibtisham, Awang Hazmi Awang-Junaidi & Ali Honaramooz

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  1. Fahar Ibtisham
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  3. Ali Honaramooz
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Correspondence to Ali Honaramooz.

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Experimental procedures involving animals conducted by our group were reviewed and approved by the University of Saskatchewan’s Institutional Animal Care and Use Committee.

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Ibtisham, F., Awang-Junaidi, A.H. & Honaramooz, A. The study and manipulation of spermatogonial stem cells using animal models. Cell Tissue Res 380, 393–414 (2020). https://doi.org/10.1007/s00441-020-03212-x

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