Male 'blind sterile' mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as 'nurse cells' essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in 'blind sterile' male mice.

中文翻译：

---

TBC1D20缺乏症通过引发小鼠不可逆的内质网应激来诱导支持细胞凋亡。

具有致病性TBC1域家族成员20（TBC1D20）缺陷的雄性“盲无菌”小鼠不育，其生殖细胞凋亡过多，精子发生停滞在精子期。睾丸支持细胞是正常精子发生必不可少的“护士细胞”，但是至今尚不清楚TBC1D20缺乏症在小鼠支持细胞中的作用和相应的分子机制。在本研究中，确定了睾丸的组织病理学和支持细胞的增殖和凋亡，并通过蛋白质印迹研究了相应的分子机制。我们的数据表明，TBC1D20表现出丰富的睾丸表达模式，其表达水平与精子发生成正相关。TBC1D20组装在高尔基体和内质网中，并广泛表达于各种生殖细胞亚型和支持细胞。Sertoli细胞中的TBC1D20缺乏导致细胞凋亡率过高和G1 / S阻滞。caspase-12激活导致TBC1D20缺陷的Sertoli细胞凋亡增加。缺乏TBC1D20的Sertoli细胞具有异常的高尔基体-内质网结构，这导致内质网应激，导致细胞周期停滞和过度凋亡。提示TBC1D20缺乏会触发不可逆的内质网应激，从而导致G1 / S停滞和缺乏TBC1D20的Sertoli细胞过度凋亡，而Sertoli细胞中的TBC1D20缺乏也可能导致``盲无菌''雄性小鼠的不育表型。Sertoli细胞中的TBC1D20缺乏导致细胞凋亡率过高和G1 / S阻滞。caspase-12激活导致TBC1D20缺陷的Sertoli细胞凋亡增加。缺乏TBC1D20的Sertoli细胞具有异常的高尔基体-内质网结构，这导致内质网应激，导致细胞周期停滞和过度凋亡。提示TBC1D20缺乏会触发不可逆的内质网应激，从而导致G1 / S停滞和缺乏TBC1D20的Sertoli细胞过度凋亡，而Sertoli细胞中的TBC1D20缺乏也可能导致``盲无菌''雄性小鼠的不育表型。Sertoli细胞中的TBC1D20缺乏导致细胞凋亡率过高和G1 / S阻滞。caspase-12激活导致TBC1D20缺陷的Sertoli细胞凋亡增加。缺乏TBC1D20的Sertoli细胞具有异常的高尔基体-内质网结构，这导致内质网应激，导致细胞周期停滞和过度凋亡。提示TBC1D20缺乏会触发不可逆的内质网应激，从而导致G1 / S停滞和缺乏TBC1D20的Sertoli细胞过度凋亡，而Sertoli细胞中的TBC1D20缺乏也可能导致``盲无菌''雄性小鼠的不育表型。缺乏TBC1D20的Sertoli细胞具有异常的高尔基体-内质网结构，这导致内质网应激，导致细胞周期停滞和过度凋亡。提示TBC1D20缺乏会触发不可逆的内质网应激，从而导致G1 / S停滞和缺乏TBC1D20的Sertoli细胞过度凋亡，而Sertoli细胞中的TBC1D20缺乏也可能导致``盲无菌''雄性小鼠的不育表型。缺乏TBC1D20的Sertoli细胞具有异常的高尔基体-内质网结构，这导致内质网应激，导致细胞周期停滞和过度凋亡。提示TBC1D20缺乏会触发不可逆的内质网应激，从而导致G1 / S停滞和缺乏TBC1D20的Sertoli细胞过度凋亡，而Sertoli细胞中的TBC1D20缺乏也可能导致``盲无菌''雄性小鼠的不育表型。