Reconstructing The Testicular Niche: Mechanisms and Translational Perspectives of Stem Cell-derived Testicular Organoids

Xia DONG; Tai-Zeng ZHOU; Lin-Yuan SHEN; Li ZHU; Mai-Lin GAN

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Reconstructing The Testicular Niche: Mechanisms and Translational Perspectives of Stem Cell-derived Testicular Organoids

VernacularTitle:重建睾丸微环境：干细胞衍生睾丸类器官的机制和转化应用前景
Author: Xia DONG ¹ ; Tai-Zeng ZHOU ¹ ; Lin-Yuan SHEN ¹ ; Li ZHU ¹ ; Mai-Lin GAN ¹
Author Information

1. State Key Laboratory of Swine and Poultry Breeding Industry, Key Laboratory of Agricultural Bioinformatics, Ministry of Education, Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, Farm Animal Germplasm Resources and Biotech Breeding Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China
Publication Type:Journal Article
Keywords: pluripotent stem cells; sex determination; testicular organoid; in vitro gametogenesis; reproductive microenvironment
From: Progress in Biochemistry and Biophysics 2026;53(8):2242-2246
CountryChina
Language:English
Abstract: Mammalian male germline development depends on a specialized gonadal somatic microenvironment. However, itsin vitro reconstruction remains challenging. Major barriers include the generation of appropriate supporting-cell lineages, organized tissue architecture, and culture conditions that sustain germ-cell maturation. Yoshino et al. established a mouse pluripotent stem cell-derived testicular organoid model. This model reconstitutes the sex-determining region Y (Sry)-SRY-box transcription factor 9 (Sox9)‑mediated sex-determination program and generates testicular somatic cell-like cells (TesLCs). When assembled with primordial germ cell-like cells (PGCLCs), TesLCs formed seminiferous tubule-like structures and supported male germline progression toward prospermatogonia and germline stem cell-like cells (GSCLCs). After transplantation into infertile recipient testes, organoid-derived GSCLCs produced fertilization-competent sperm and generated fertile offspring. The major significance of this work extends beyond sperm production. It integrates sex determination, germ-cell fate transition, and testicular niche self-organization into an experimentally tractable organoid system. This commentary discusses the technical strategy, sex-determination mechanism, value of testicular niche reconstruction, and translational limitations of this study. It also highlights its implications for in vitro gametogenesis, male infertility modeling, and reproductive medicine.