TBC1D20 deficiency induces Sertoli cell apoptosis by triggering irreversible endoplasmic reticulum stress in mice
| Autor: | Jing Yu, Jing Ye, Yanli Gu, Lina Cui, Wen-Lin Chang, Yaoting Gui, Minghua Li, Fangting Zhang, Zeng Zhang, Qian Ma |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
endocrine system Embryology Golgi Apparatus Sertoli cell proliferation Spermatogenesis arrest Apoptosis Mice Transgenic Biology Endoplasmic Reticulum Mice symbols.namesake Genetics medicine Animals Spermatogenesis Molecular Biology Caspase 12 Infertility Male Cell Proliferation Sertoli Cells urogenital system Endoplasmic reticulum Obstetrics and Gynecology Cell Biology Golgi apparatus Endoplasmic Reticulum Stress Sertoli cell G1 Phase Cell Cycle Checkpoints Cell biology rab1 GTP-Binding Proteins medicine.anatomical_structure Reproductive Medicine symbols Germ cell Developmental Biology |
| Zdroj: | Molecular Human Reproduction. 25:773-786 |
| ISSN: | 1460-2407 |
| DOI: | 10.1093/molehr/gaz057 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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