Roles of Spermatogonial Stem Cells in Spermatogenesis and Fertility Restoration

Diao, Lei; Turek, Paul J.; John, Constance M.; Fang, Fang; Pera, Renee A. Reijo

doi:10.3389/fendo.2022.895528

Cited by 19 publications

(11 citation statements)

References 110 publications

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“…The seminiferous tubule and the interstitial tissue provide a local niche for SSCs. 362 , 363 Somatic Sertoli cells are the supporting cells in the testis, and their differentiation is regulated by waves of transcription factors SRY, SOX9, AMH, and DHH. 364 Sertoli cells finally generate and secrete specific factors for SSC development.…”

Section: Adult Germline Stem Cellsmentioning

confidence: 99%

Germline stem cells in human

Cheng

Shang

Zhou

2022

Sig Transduct Target Ther

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The germline cells are essential for the propagation of human beings, thus essential for the survival of mankind. The germline stem cells, as a unique cell type, generate various states of germ stem cells and then differentiate into specialized cells, spermatozoa and ova, for producing offspring, while self-renew to generate more stem cells. Abnormal development of germline stem cells often causes severe diseases in humans, including infertility and cancer. Primordial germ cells (PGCs) first emerge during early embryonic development, migrate into the gentile ridge, and then join in the formation of gonads. In males, they differentiate into spermatogonial stem cells, which give rise to spermatozoa via meiosis from the onset of puberty, while in females, the female germline stem cells (FGSCs) retain stemness in the ovary and initiate meiosis to generate oocytes. Primordial germ cell-like cells (PGCLCs) can be induced in vitro from embryonic stem cells or induced pluripotent stem cells. In this review, we focus on current advances in these embryonic and adult germline stem cells, and the induced PGCLCs in humans, provide an overview of molecular mechanisms underlying the development and differentiation of the germline stem cells and outline their physiological functions, pathological implications, and clinical applications.

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Section: Adult Germline Stem Cellsmentioning

confidence: 99%

Germline stem cells in human

Cheng

Shang

Zhou

2022

Sig Transduct Target Ther

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“…Our results were in accordance with previous studies that proved that stem cells can be developed into germ cells, and spermatogenesis happened after transplanting differentiated germ cells from MSCs into sterile animals testes, and the animals eventually generated spermatozoon primordial germ cells or germ-like cells, which can be created by various cell sources of stem cells such as bone marrow stem cells ( Marques-Mari et al, 2009 ; Vlajković et al, 2012 ; Ghasemzadeh-Hasankolaei et al, 2016 ; Salem et al, 2019 ). All of our data suggest that MSCs can protect against the cytotoxic effects of CYP in producing infertility in male chemotherapy patients that may be by two different mechanisms which may be by preserving pre-existing spermatogonial stem cells (SSCs) or trans-differentiating into SSC-like cells to generate spermatocytes ( Kubota and Brinster, 2018 ; Ibtisham and Honaramooz, 2020 ; Diao et al, 2022 ).…”

Section: Discussionmentioning

confidence: 94%

“…Throughout the life of a male, the spermatogenesis process sustains the generation of spermatozoa, the last cell carrier of genetic substances ( Mruk and Cheng, 2004 ; Smith and Walker, 2014 ; Diao et al, 2022 ). Testicular damage is a significant issue following the treatment of different cancers, and infertility triggered by chemotherapy is a problematic issue that patients must deal with, and it may also have a negative influence on their family life ( Cao et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…In this scenario, MSCs appear to be promising prospects for reducing the negative effects of anti-cancer medications ( Gomez-Salazar et al, 2020 ). Stem cells might help to restore spermatogenesis in two ways: sustaining pre-existing spermatogonial stem cells (SSCs) or transdifferentiating into SSC-like cells to create spermatocytes ( Diao et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic potential of bone marrow mesenchymal stem cells in cyclophosphamide-induced infertility

et al. 2023

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Cancer is a deadly disease characterized by abnormal cell proliferation. Chemotherapy is one technique of cancer treatment. Cyclophosphamide (CYP) is the most powerful chemotherapy medication, yet it has serious adverse effects. It is an antimitotic medicine that regulates cell proliferation and primarily targets quickly dividing cells, and it has been related to varying levels of infertility in humans. In the current study, we assessed the biochemical, histological, and microscopic evaluations of testicular damage following cyclophosphamide administration. Further, we have explored the potential protective impact of mesenchymal stem cell (MSCs) transplantation. The biochemical results revealed that administration of cyclophosphamide increased serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), while it decreased serum concentrations of free testosterone hormone (TH), testicular follicle-stimulating hormone, luteinizing hormone, and free testosterone hormone concentrations, testicular total antioxidant capacity (TAC), and testicular activity of superoxide dismutase (SOD) enzyme. The histology and sperm examinations revealed that cyclophosphamide induced destruction to the architectures of several tissues in the testes, which drastically reduced the Johnsen score as well as the spermatogenesis process. Surprisingly, transplantation of mesenchymal stem cell after cyclophosphamide administration altered the deterioration effect of cyclophosphamide injury on the testicular tissues, as demonstrated by biochemical and histological analysis. Our results indicated alleviation of serum and testicular sex hormones, as well as testicular oxidative stress markers (total antioxidant capacity and superoxide dismutase activity), and nearly restored the normal appearance of the testicular tissues, Johnsen score, and spermatogenesis process. In conclusion, our work emphasizes the protective pharmacological use of mesenchymal stem cell to mitigate the effects of cyclophosphamide on testicular tissues that impair the spermatogenesis process following chemotherapy. These findings indicate that transferring mesenchymal stem cell to chemotherapy patients could significantly improve spermatogenesis.

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“…Spermatogonial stem cells (SSCs) are crucial for initiating and maintaining spermatogenesis, the process of sperm production in the testes (Diao, Turek, John, Fang, & Reijo Pera, 2022). This process begins at puberty and continues throughout a man's life.…”

Section: Introductionmentioning

confidence: 99%

Riluzole reverses blood-testis barrier loss to rescue chemotherapy-induced male infertility by binding to TRPC

Huang,

Xia,

Lin

et al. 2024

Preprint

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Cancer treatments, including cytotoxic therapy, often result in male infertility, necessitating the development of safe and effective strategies to preserve male reproductive potential during chemotherapy. Notably, our study uncovers the potential of repurposing riluzole, an FDA-approved drug for amyotrophic lateral sclerosis (ALS), in enhancing spermatogenesis. Hence, this research aims to explore the feasibility of utilizing riluzole to alleviate male infertility induced by busulfan (BSF), a commonly used chemotherapy drug. We established a BSF-induced oligospermia model in 4-week-old male mice and found that riluzole could effectively countered the detrimental effects of BSF on sperm production in mice with oligospermia. By restoring blood-testis barrier (BTB) functionality, riluzole improves sperm quality and reduces testicular atrophy. Through transcriptomic and molecular docking analyses, we identify transient receptor potential canonical subfamily member 5 (TRPC5) as a potential target for riluzole-mediated regulation of blood-testis barrier function. These findings propose riluzole as a promising therapeutic option for chemotherapy-induced male infertility, thereby addressing the fertility challenges associated with cancer treatments. Moreover, repurposing riluzole could streamline the drug development process, providing a cost-effective approach with reduced risk compared to developing entirely new drugs.

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Roles of Spermatogonial Stem Cells in Spermatogenesis and Fertility Restoration

Cited by 19 publications

References 110 publications

Germline stem cells in human

Germline stem cells in human

Therapeutic potential of bone marrow mesenchymal stem cells in cyclophosphamide-induced infertility

Riluzole reverses blood-testis barrier loss to rescue chemotherapy-induced male infertility by binding to TRPC

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