Male Germline Stem Cells

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: closed (20 March 2022) | Viewed by 10642

Special Issue Editor

Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N5B4, Canada
Interests: spermatogonial stem cells; testis tissue xenografting; in vitro spermatogenesis; testis organoids

Special Issue Information

Dear Colleagues,

Pioneering research in the past three decades has transformed our knowledge of male germline stem cells (MGSCs). Given the intricate form and function of the testis in situ, the advent of innovative in vitro and in vivo models for testicular cells and tissue has provided powerful experimental tools to allow novel discoveries. As a result, new perspectives and avenues of basic and applied research have been introduced, leading to our expanding understanding of the biology and potential applications of MGSCs. The intent of this Special Issue is to provide a forum to highlight some of the salient advances in the study, manipulation, and application of MGSCs. I am thrilled to invite my esteemed colleagues to submit their highest-quality original research and/or review articles related to any aspect of MGSC biology or application, to be included in this invaluable collection.

Potential topics include but are not limited to:

  • Original discoveries related to the self-renewal or proliferation of MGSCs;
  • New insights about the regulation of their stemness;
  • Advances in their identity and molecular characterization;
  • Updates on their culture, preservation or transgenesis;
  • Advances in understanding their pluripotency/multipotency;
  • Overview of in vitro or in vivo models to study or manipulate MGSCs;
  • Progress in their application in infertility treatment;
  • Potential application of MGSC-derived cells in regenerative medicine;
  • Application of MGSCs in animal transgenesis or genetic conservation;
  • Current status and future potential of their use for in vitro spermatogenesis;
  • Progress in their development in testicular 3D cultures, organoids, grafts, or implants.

Prof. Dr. Ali Honaramooz
Guest Editor

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Keywords

  • spermatogonial stem cells (SSCs)
  • germline stem cells
  • undifferentiated spermatogonia
  • gonocytes
  • germ cells
  • spermatogenesis
  • progenitor cells
  • prospermatogonia
  • primordial germ cells

Published Papers (4 papers)

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Research

27 pages, 46936 KiB  
Article
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine- and Paracrine-Dependent Manners
by Lucas B. Doretto, Arno J. Butzge, Rafael T. Nakajima, Emanuel R. M. Martinez, Beatriz Marques de Souza, Maira da Silva Rodrigues, Ivana F. Rosa, Juliana M. B. Ricci, Aldo Tovo-Neto, Daniel F. Costa, Guilherme Malafaia, Changwei Shao and Rafael H. Nóbrega
Cells 2022, 11(8), 1295; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11081295 - 11 Apr 2022
Cited by 5 | Viewed by 2678
Abstract
Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GDNF Family Receptor α1-GFRα1) are well known to mediate spermatogonial stem cell (SSC) proliferation and survival in mammalian testes. In nonmammalian species, Gdnf and Gfrα1 orthologs have been found but their functions remain poorly [...] Read more.
Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GDNF Family Receptor α1-GFRα1) are well known to mediate spermatogonial stem cell (SSC) proliferation and survival in mammalian testes. In nonmammalian species, Gdnf and Gfrα1 orthologs have been found but their functions remain poorly investigated in the testes. Considering this background, this study aimed to understand the roles of the Gdnf-Gfrα1 signaling pathway in zebrafish testes by combining in vivo, in silico and ex vivo approaches. Our analysis showed that zebrafish exhibit two paralogs for Gndf (gdnfa and gdnfb) and its receptor, Gfrα1 (gfrα1a and gfrα1b), in accordance with a teleost-specific third round of whole genome duplication. Expression analysis further revealed that both ligands and receptors were expressed in zebrafish adult testes. Subsequently, we demonstrated that gdnfa is expressed in the germ cells, while Gfrα1a/Gfrα1b was detected in early spermatogonia (mainly in types Aund and Adiff) and Sertoli cells. Functional ex vivo analysis showed that Gdnf promoted the creation of new available niches by stimulating the proliferation of both type Aund spermatogonia and their surrounding Sertoli cells but without changing pou5f3 mRNA levels. Strikingly, Gdnf also inhibited late spermatogonial differentiation, as shown by the decrease in type B spermatogonia and down-regulation of dazl in a co-treatment with Fsh. Altogether, our data revealed that a germ cell-derived factor is involved in maintaining germ cell stemness through the creation of new available niches, supporting the development of spermatogonial cysts and inhibiting late spermatogonial differentiation in autocrine- and paracrine-dependent manners. Full article
(This article belongs to the Special Issue Male Germline Stem Cells)
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13 pages, 3430 KiB  
Article
SETDB1 Regulates Porcine Spermatogonial Adhesion and Proliferation through Modulating MMP3/10 Transcription
by Ruifang Liu, Zidong Liu, Ming Guo, Wenxian Zeng and Yi Zheng
Cells 2022, 11(3), 370; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030370 - 22 Jan 2022
Cited by 4 | Viewed by 2597
Abstract
The transition from gonocytes into spermatogonia takes place during the homing process. A subpopulation of undifferentiated spermatogonia in niche then shifts to spermatogonial stem cells (SSCs), accompanied by the self-renewal ability to maintain life-long fertility in males. Enormous changes in cell morphology, gene [...] Read more.
The transition from gonocytes into spermatogonia takes place during the homing process. A subpopulation of undifferentiated spermatogonia in niche then shifts to spermatogonial stem cells (SSCs), accompanied by the self-renewal ability to maintain life-long fertility in males. Enormous changes in cell morphology, gene expression, and epigenetic features have been reported during spermatogenesis. However, little is known about the difference of these features in SSCs during aging. Here, we examined the dynamics of SET domain bifurcated 1 (SETDB1) expression in porcine testes. SETDB1 was expressed in postnatal undifferentiated spermatogonia, while gradually disappeared after being packed within the basal compartment of seminiferous tubules. In addition, the cell-adhesion ability, proliferative activity, and trimethylation of the histone H3 lysine 9 (H3K9me3) level were significantly altered in SETDB1-deficient porcine SSCs. Moreover, the matrix metalloproteinases 3/10 (MMP3/10) was upregulated at both mRNA and protein levels. These results illustrate the significance of SETDB1 in modulating early male germ cell development. Full article
(This article belongs to the Special Issue Male Germline Stem Cells)
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22 pages, 9192 KiB  
Article
Neonatal Porcine Germ Cells Dedifferentiate and Display Osteogenic and Pluripotency Properties
by Mohammad Amin Fayaz, Gustavo dos Santos Rosa and Ali Honaramooz
Cells 2021, 10(11), 2816; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10112816 - 20 Oct 2021
Viewed by 2010
Abstract
Gonocytes are progenitors of spermatogonial stem cells in the neonatal testis. We have previously shown that upon culturing, neonatal porcine gonocytes and their colonies express germ cell and pluripotency markers. The objectives of present study were to investigate in vitro trans-differentiation potential of [...] Read more.
Gonocytes are progenitors of spermatogonial stem cells in the neonatal testis. We have previously shown that upon culturing, neonatal porcine gonocytes and their colonies express germ cell and pluripotency markers. The objectives of present study were to investigate in vitro trans-differentiation potential of porcine gonocytes and their colonies into cells from three germinal layers, and to assess pluripotency of cultured gonocytes/colonies in vivo. For osteogenic and tri-lineage differentiation, cells were incubated in regular culture media for 14 and 28 days, respectively. Cells were cultured for an additional 14 days for osteogenic differentiation or 7 days for differentiation into derivates of the three germinal layers. Osteogenic differentiation of cells and colonies was verified by Alizarin Red S staining and tri-lineage differentiation was confirmed using immunofluorescence and gene expression analyses. Furthermore, upon implantation into recipient mice, the cultured cells/colonies developed teratomas expressing markers of all three germinal layers. Successful osteogenic differentiation from porcine germ cells has important implications for bone regeneration and matrix formation studies. Hence, gonocytes emerge as a promising source of adult pluripotent stem cells due to the ability to differentiate into all germinal layers without typical biosafety risks associated with viral vectors or ethical implications. Full article
(This article belongs to the Special Issue Male Germline Stem Cells)
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21 pages, 4726 KiB  
Article
Loss of Ubiquitin Carboxy-Terminal Hydrolase L1 Impairs Long-Term Differentiation Competence and Metabolic Regulation in Murine Spermatogonial Stem Cells
by Whitney F. Alpaugh, Anna L. Voigt, Rkia Dardari, Lin Su, Iman Al Khatib, Wisoo Shin, Taylor M. Goldsmith, Krysta M. Coyle, Lin A. Tang, Timothy E. Shutt, Claudia Klein, Jeff Biernaskie and Ina Dobrinski
Cells 2021, 10(9), 2265; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10092265 - 31 Aug 2021
Cited by 11 | Viewed by 2459
Abstract
Spermatogonia are stem and progenitor cells responsible for maintaining mammalian spermatogenesis. Preserving the balance between self-renewal of spermatogonial stem cells (SSCs) and differentiation is critical for spermatogenesis and fertility. Ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) is highly expressed in spermatogonia of many species; however, its [...] Read more.
Spermatogonia are stem and progenitor cells responsible for maintaining mammalian spermatogenesis. Preserving the balance between self-renewal of spermatogonial stem cells (SSCs) and differentiation is critical for spermatogenesis and fertility. Ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) is highly expressed in spermatogonia of many species; however, its functional role has not been identified. Here, we aimed to understand the role of UCH-L1 in murine spermatogonia using a Uch-l1−/− mouse model. We confirmed that UCH-L1 is expressed in undifferentiated and early-differentiating spermatogonia in the post-natal mammalian testis. The Uch-l1−/− mice showed reduced testis weight and progressive degeneration of seminiferous tubules. Single-cell transcriptome analysis detected a dysregulated metabolic profile in spermatogonia of Uch-l1−/− compared to wild-type mice. Furthermore, cultured Uch-l1−/− SSCs had decreased capacity in regenerating full spermatogenesis after transplantation in vivo and accelerated oxidative phosphorylation (OXPHOS) during maintenance in vitro. Together, these results indicate that the absence of UCH-L1 impacts the maintenance of SSC homeostasis and metabolism and impacts the differentiation competence. Metabolic perturbations associated with loss of UCH-L1 appear to underlie a reduced capacity for supporting spermatogenesis and fertility with age. This work is one step further in understanding the complex regulatory circuits underlying SSC function. Full article
(This article belongs to the Special Issue Male Germline Stem Cells)
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