Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?
Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?
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DOI：
10.1016/j.semcdb.2016.01.003
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发表时间：
2016-11
影响因子：
7.3
通讯作者：
Cheng CY
中科院分区：
文献类型：
--
作者：
Li N;Mruk DD;Lee WM;Wong CK;Cheng CY
已知从啮齿动物或人类分离并在体外培养的支持细胞建立功能性紧密连接（TJ）-渗透性屏障，其模拟体内的血-睾丸屏障（BTB）。该模型已被研究人员广泛用于研究TJ和BTB的生物学。研究表明，环境毒物（例如，使用该体外模型，在体内研究中可重现全氟辛烷磺酸（PFOS）、双酚A（BPA）和镉）的破坏作用，从而诱导支持细胞损伤。因此，这种体外系统提供了一种方便的方法来探测毒素诱导的睾丸损伤的分子机制，但也提供了新的见解，在理解精子发生，如细胞粘附，精子细胞运输的生物学，和其他。在此，我们提供了一个简短的和关键的审查的基础上，使用这个在体外模型的支持细胞培养使用原代细胞分离的啮齿动物睾丸与人类监测环境毒物介导的支持细胞损伤的研究，这一信息是相关的分子机制，调节精子发生。总之，最近的研究结果表明，环境毒物对支持细胞发挥其作用，通过其对支持细胞肌动蛋白和/或微管为基础的细胞骨架的作用，诱导睾丸损伤。这些作用通过其对肌动蛋白和/或微管结合蛋白的破坏性作用介导。支持细胞还利用这些肌动蛋白结合蛋白的差异时空表达来赋予BTB可塑性以调节生殖细胞跨BTB的运输。
Sertoli cells isolated from rodents or humans and cultured in vitro are known to establish a functional tight junction (TJ)-permeability barrier that mimics the blood-testis barrier (BTB) in vivo. This model has been widely used by investigators to study the biology of the TJ and the BTB. Studies have shown that environmental toxicants (e.g., perfluorooctanesulfonate (PFOS), bisphenol A (BPA) and cadmium) that exert their disruptive effects to induce Sertoli cell injury using this in vitro model are reproducible in studies in vivo. Thus, this in vitro system provides a convenient approach to probe the molecular mechanism(s) underlying toxicant-induced testis injury but also to provide new insights in understanding spermatogenesis, such as the biology of cell adhesion, spermatid transport, and others. Herein, we provide a brief and critical review based on studies using this in vitro model of Sertoli cell cultures using primary cells isolated from rodent testes versus humans to monitor environmental toxicant-mediated Sertoli cell injury, and this information is relevant to the molecular mechanisms that regulate spermatogenesis. In short, recent findings have shown that environmental toxicants exert their effects on Sertoli cells to induce testis injury through their action on Sertoli cell actin- and/or microtubule-based cytoskeleton. These effects are mediated via their disruptive effects on actin- and/or microtubule-binding proteins. Sertoli cells also utilize differential spatiotemporal expression of these actin binding proteins to confer plasticity to the BTB to regulate germ cell transport across the BTB.