TBC1D20 Is Essential for Mouse Blood-Testis Barrier Integrity Through Maintaining the Epithelial Phenotype and Modulating the Maturation of Sertoli Cells
TBC1D20 Is Essential for Mouse Blood-Testis Barrier Integrity Through Maintaining the Epithelial Phenotype and Modulating the Maturation of Sertoli Cells
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TBC1D20 通过维持上皮表型和调节支持细胞的成熟，对于小鼠血睾屏障的完整性至关重要
DOI：
10.1007/s43032-020-00156-z
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发表时间：
2020-01-28
影响因子：
2.9
通讯作者：
Gui, Yaoting
中科院分区：
文献类型：
--
作者：
Cui, Lina;Gu, Yanli;Gui, Yaoting
支持细胞不仅与生精上皮中的生殖细胞直接相互作用，而且通过构成血-睾丸屏障(BTB)结构为精子发生创造有利的环境，对精子发生具有重要作用。盲目不育(Bs)雄性小鼠不育，生殖细胞过度凋亡，精子发生停滞。TBC1D20(Tbc1结构域家族成员20)缺失已被确定为bs小鼠的致病突变。然而，TBC1D20功能丧失是否也损害了BTB的完整性，从而进一步导致BS雄性小鼠精子发生的失败，目前尚不清楚。在目前的研究中，生物素示踪分析和透射电子显微镜显示BS睾丸中的BTB完整性严重破坏。与野生型支持细胞相比，体外培养的支持细胞的BTB成分被E-钙粘蛋白、ZO-1、β-连环蛋白和Claudin 11的下调所干扰。F-肌动蛋白的明显重排表明，在TBC1D20缺陷的支持细胞中，支持细胞的上皮-间质平衡被破坏。支持细胞维持精原干细胞克隆形成的能力也明显受限。此外，BS支持细胞中性别决定区域Y box 9和WT1的表达减少以及波形蛋白的表达增加，表明TBC1D20功能丧失抑制了bs支持细胞的分化进程。总之，TBC1D20功能的丧失阻碍了成年支持细胞的成熟，导致了BTB完整性的受损，这进一步与bs雄性小鼠的不育表型有关。
Sertoli cells are important for spermatogenesis not only by directly interacting with germ line cells in the seminiferous epithelium but also by constituting the blood-testis barrier (BTB) structure to create a favorable environment for spermatogenesis. Blind sterile (bs) male mice are infertile, with excessive germ cell apoptosis and spermatogenesis arrest. TBC1D20 (TBC1 domain family member 20) deficiency has been identified as the causative mutation in bs mice. However, whether TBC1D20 loss of function also impairs BTB integrity, which further contributes to the failed spermatogenesis of bs male mice, remains unclear. In the present study, biotin tracer assay and transmission electron microscopy showed severely disrupted BTB integrity in bs testes. Compared to the wild-type Sertoli cells, BTB components of cultured bs Sertoli cells in vitro was perturbed with downregulation of E-cadherin, ZO-1, beta-catenin, and Claudin 11. The obvious rearrangement of F-actin indicated disrupted epithelial-mesenchymal balance in TBC1D20-deficient Sertoli cells. The ability of bs Sertoli cells to maintain the clone formation of spermatogonia stem cells was also obviously limited. Furthermore, the decreasing of SOX9 (sex-determining region Y box 9) and WT1 (Wilms' tumor 1) and increasing of vimentin in bs Sertoli cells indicated that TBC1D20 loss of function attenuated the differentiation progression of bs Sertoli cells. In summary, TBC1D20 loss of function impedes the maturation of adult Sertoli cells and resulted in impaired BTB integrity, which is further implicated in the infertile phenotype of bs male mice.