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TBC1D20 deficiency induces Sertoli cell apoptosis by triggering irreversible endoplasmic reticulum stress in mice
- Source :
- Molecular Human Reproduction. 25:773-786
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14602407
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Molecular Human Reproduction
- Accession number :
- edsair.doi.dedup.....e180f2457d61a50b45141d4c4dc7515f