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Review
. 2024 Sep 11;15(1):294.
doi: 10.1186/s13287-024-03893-z.

Microenvironment of spermatogonial stem cells: a key factor in the regulation of spermatogenesis

Wei Liu #  1   2 , Li Du #  3 , Junjun Li  1 , Yan He  4 , Mengjie Tang  5
Affiliations
Review

Microenvironment of spermatogonial stem cells: a key factor in the regulation of spermatogenesis

Wei Liu et al. Stem Cell Res Ther. .

Abstract

Spermatogonial stem cells (SSCs) play a crucial role in the male reproductive system, responsible for maintaining continuous spermatogenesis. The microenvironment or niche of SSCs is a key factor in regulating their self-renewal, differentiation and spermatogenesis. This microenvironment consists of multiple cell types, extracellular matrix, growth factors, hormones and other molecular signals that interact to form a complex regulatory network. This review aims to provide an overview of the main components of the SSCs microenvironment, explore how they regulate the fate decisions of SSCs, and discuss the potential impact of microenvironmental abnormalities on male reproductive health.

Keywords: Differentiation; Microenvironment; Niche; Self-renewal; Spermatogenesis; Spermatogonial stem cells.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Schematic diagram of testicular spermatogenesis. The formation of spermatogonia differs between mouse and human spermatogonia, with type A spermatogonia in mice mainly divided into Asingle, Aparied, Aaligned, and A1–A4 spermatogonia; whereas human type A spermatogonia are divided into Adark and Apale spermatogonia
Fig. 2
Fig. 2
Regulatory Network of SSC Self-Renewal by Sertoli Cells. Sertoli cells regulate SSC self-renewal through key signaling pathways such as GDNF, which is essential for SSC maintenance, and FGF2, which synergizes with GDNF to enhance SSC proliferation. ETV5 aids in the transcriptional regulation of SSC self-renewal genes. Other signaling molecules and pathways also contribute to maintaining the balance between SSC self-renewal and differentiation
Fig. 3
Fig. 3
Regulatory network of SSC differentiation by Sertoli cells. VEGFA165B regulates SSC differentiation by binding to VEGFR, and both SCF and KITL are involved in SSC differentiation by binding to c-kit. Also LRH1, WT1, Cx43, Erbb4/Nrg1, and Rdh10 regulate SSC differentiation
Fig. 4
Fig. 4
Regulation of SSCs by Leydig cells, PMCs, VECs, and macrophage. Leydig cells regulate SSCs mainly by secreting CSF1, ESR2, and IGF1. PMCs affect SSCs mainly by secreting AR, GDNF, CSF1, and pnliprp2. VECs affect SSCs by secreting GDNF, and macrophages regulate SSCs by secreting CSF1 and NR2C2
Fig. 5
Fig. 5
Four approaches to explore microenvironmental regulation of SSCs. The four research methods mainly include in vivo experiments (A), in vitro transplantation experiments (B), establishment of in vitro co-culture systems (C), and construction of testicular organoids (D)
See this image and copyright information in PMC

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