The significant rise in male infertility disorders over the years has led to extensive research efforts to recapitulate the process of male gametogenesis in vitro and to identify essential mechanisms involved in spermatogenesis, notably for clinical applications. A promising technology to bridge this research gap is organ-on-chip (OoC) technology, which has gradually transformed the research landscape in ART and offers new opportunities to develop advanced in vitro culture systems. With exquisite control on a cell or tissue microenvironment, customized organ-specific structures can be fabricated in in vitro OoC platforms, which can also simulate the effect of in vivo vascularization. Dynamic cultures using microfluidic devices enable us to create stimulatory effect and non-stimulatory culture conditions. Noteworthy is that recent studies demonstrated the potential of continuous perfusion in OoC systems using ex vivo mouse testis tissues. Here we review the existing literature and potential applications of such OoC systems for male reproduction in combination with novel bio-engineering and analytical tools. We first introduce OoC technology and highlight the opportunities offered in reproductive biology in general. In the subsequent section, we discuss the complex structural and functional organization of the testis and the role of the vasculature-associated testicular niche and fluid dynamics in modulating testis function. Next, we review significant technological breakthroughs in achieving in vitro spermatogenesis in various species and discuss the evidence from microfluidics-based testes culture studies in mouse. Lastly, we discuss a roadmap for the potential applications of the proposed testis-on-chip culture system in the field of primate male infertility, ART and reproductive toxicology.

中文翻译：

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雄性生殖中的微流体：灵长类动物睾丸组织的离体培养是否是ART或毒理学研究的未来策略？

多年来，男性不育症的显着增加导致了广泛的研究工作，以概括体外的男性配子发生过程，并确定参与精子发生的重要机制，特别是在临床应用中。缩小这一研究差距的一项有前途的技术是片上器官（OoC）技术，该技术逐渐改变了ART的研究领域，并为开发先进的体外培养系统提供了新的机会。通过对细胞或组织微环境的精确控制，可以在体外OoC平台上制造定制的器官特异性结构，该平台还可以模拟体内血管化的效果。使用微流控设备的动态培养使我们能够创造刺激作用和非刺激培养条件。值得注意的是，最近的研究表明使用离体小鼠睾丸组织在OoC系统中进行连续灌注的潜力。在这里，我们结合新的生物工程和分析工具，回顾了此类OoC系统用于男性生殖的现有文献和潜在应用。我们首先介绍OoC技术，并着重介绍生殖生物学的一般机会。在接下来的部分中，我们将讨论睾丸的复杂结构和功能组织，以及与脉管系统相关的睾丸生境和流体动力学在调节睾丸功能中的作用。接下来，我们回顾了实现各种物种体外精子发生的重大技术突破，并讨论了基于微流控技术的小鼠睾丸培养研究的证据。最后，