合成生物学

• 特约评述 •    

睾丸类器官在体外精子发生中的研究进展

张博航, 祁晓萱, 袁艳   

  1. 生殖医学与子代健康全国重点实验室,南京医科大学,江苏 南京 211166
  • 收稿日期:2023-11-30 修回日期:2024-03-05 出版日期:2024-03-11
  • 通讯作者: 袁艳
  • 作者简介:张博航(1999—),男,博士研究生。研究方向为精子发生过程中相关机制的研究。E-mail:zhangbohang2018@163.com
    袁艳(1987—),女,博士,教授博士生导师。国自然优秀青年基金获得者,国家重点研发计划青年首席,中国生理学会生殖分会委员,江苏省青年医学人才,江苏省发育生物学会理事。长期致力于体外男性生育力重构,包括胚胎干细胞(ESC)和诱导多能干细胞(iPSC)分化、睾丸类器官重构及相关机制研究,以通讯作者/第一作者在Cell Stem Cell、Cell Research、Cell Proliferation等国际刊物上发表多篇SCI论文。授权发明专利8项。E-mail:yuanyan@njmu.edu.cn
  • 基金资助:
    国家重点研发计划(2022YFC2702800);国家自然科学基金(82122025)

Advancements in testicular organoids for in vitro spermatogenesis

Bohang ZHANG, Xiaoxuan QI, Yan YUAN   

  1. State Key Laboratory of Reproductive Medicine and Offspring Health,Nanjing Medical University,Nanjing 211166,Jiangsu,China
  • Received:2023-11-30 Revised:2024-03-05 Online:2024-03-11
  • Contact: Yan YUAN

摘要:

随着全球不孕不育问题的日益增加,特别是男性不育症的比例逐年上升,睾丸类器官的研究为这一领域提供了新的希望和策略。本综述全面探讨了睾丸类器官在模拟自然生精环境、深入探究精子发生机制,以及应对男性生殖健康挑战中的应用。首先,介绍了睾丸的生理功能和精子发生过程的重要性,关注了睾丸组织体外培养和睾丸细胞重聚类器官的技术及其研究进展。其次,探讨了睾丸类器官在探究分子机制、药物筛选和毒性评估及男性生育力保存方面的潜在应用。最后,对当前方法的局限性和未来研究方向进行了讨论,特别是在提高体外环境下精子质量和成熟度方面的研究成果。尽管睾丸微环境复杂,在体外完整模拟人类精子发生仍面临挑战,但睾丸类器官领域的不断发展有望为临床生殖医学和男性健康研究提供新的解决方案。

关键词: 睾丸类器官, 精子发生, 生殖医学, 睾丸微环境, 应用

Abstract:

As the global issue of infertility continues to escalate, particularly with the increasing incidence of male infertility, research in testicular organoids offers new hope and strategies in this field. This review comprehensively discusses the application of testicular organoids in simulating the natural sperm-producing environment, delving into the mechanisms of spermatogenesis, and addressing challenges in male reproductive health. Firstly, we introduce the cellular composition, physiological functions, and the complete process of spermatogenesis within the testicular organ, emphasizing the crucial role of the testicular somatic cell microenvironment in normal testicular development and sperm production. Subsequently, we provide a comprehensive review of the construction of in vitro spermatogenesis systems and the associated research progress through techniques such as testicular tissue culture and reconstruction of testicular organoids in vivo. Moreover, testicular organoids, as a system mimicking spermatogenesis environments in vitro, exhibit significant potential in exploring molecular mechanisms, drug screening and toxicity assessment, as well as preserving and restoring male fertility. Finally, we discuss the limitations of current research in the field of testicular organoids and future research directions. Challenges include accurately simulating the physiological processes of the testis in vitro and improving the quality of sperm obtained in vitro for clinical applications. Future research directions involve delving into the complex interactions between germ cells and somatic cells, aiming to better simulate the testicular microenvironment in vitro, and striving towards safe and effective translation of these research findings into clinical applications for treating male infertility. Additionally, we should ensure that the genetic stability and functionality of germ cells cultured in vitro meet the requirements for clinical applications, and pay attention to ethical issues related to it. Despite the complexity of the testicular microenvironment and the challenges in fully replicating human spermatogenesis in vitro, the ongoing development in the field of testicular organoids holds promise for providing novel solutions in clinical reproductive medicine and male health research.

Key words: testicular organoids, spermatogenesis, reproductive medicine, testicular microenvironment, application

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