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
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四川农业大学动物科技学院,猪禽种业全国重点实验室,农业生物信息教育部重点实验室,农业农村部畜禽生物组学重点实验室, 畜禽种质资源与生物育种四川省重点实验室,成都 611130

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国家重点研发计划(2024YFF1000201),四川省科技支撑计划(2021ZDZX0008,SCCXTD-2026-08-09)和国家现代农业产业技术体系(CARS-35) 资助项目。


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

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This work was supported by grants from National Key R&D Program of China (2024YFF1000201), Sichuan Science and Technology Program (2021ZDZX0008, SCCXTD-2026-08-09), and China Agriculture Research System (CARS-35).

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    摘要:

    哺乳动物雄性生殖系发育依赖于特化的性腺体细胞微环境。然而,长期以来,体外重构这一过程一直受到多重因素限制,包括难以获得合适的支持细胞谱系、缺乏有序的空间组织结构,以及培养条件不足以维持生殖细胞成熟等。Yoshino等建立了一种小鼠多能干细胞来源的睾丸类器官模型,该模型能够重构由性别决定区域Y(sex-determining region Y,Sry)-SRY盒转录因子9(SRY-box transcription factor 9,Sox9)介导的性别决定程序,并生成睾丸体细胞样细胞(testicular somatic cell-like cells,TesLCs)。当TesLCs 与原始生殖细胞样细胞(primordial germ cell-like cells,PGCLCs)共同组装时,可形成类似曲细精管的结构,并支持雄性生殖系向前精原细胞和生殖干细胞样细胞(germline stem cell-like cells,GSCLCs)方向发育。将类器官来源的GSCLCs 移植至不育受体小鼠睾丸后,这些细胞能够产生具有受精能力的精子,并最终获得可育后代。因此,该研究的核心意义并不仅在于“产生精子”,而在于将性别决定、生殖细胞命运转换以及睾丸微环境的自组织过程整合到一个可实验操作的类器官系统中。本文将从技术策略、性别决定机制、睾丸微环境重构价值以及转化应用局限性等方面讨论该研究,并阐明其对体外配子发生、男性不育模型构建和生殖医学基础研究的启示。

    Abstract:

    Mammalian male germline development depends on a specialized gonadal somatic microenvironment. However, its in 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.

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董霞,周泰增,沈林園,朱砺,甘麦邻.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[J].生物化学与生物物理进展,2026,53(8):2242-2246 DONG Xia, ZHOU Tai-Zeng, SHEN Lin-Yuan, ZHU Li, GAN Mai-Lin. Reconstructing The Testicular Niche: Mechanisms and Translational Perspectives of Stem Cell-derived Testicular Organoids[J]. Progress in Biochemistry and Biophysics,2026,53(8):2242-2246

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历史
  • 收稿日期:2026-05-06
  • 最后修改日期:2026-07-05
  • 录用日期:2026-06-24
  • 在线发布日期: 2026-06-24
  • 出版日期: 2026-08-28
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