TBC1D20 Is Essential for Mouse Blood–Testis Barrier Integrity Through Maintaining the Epithelial Phenotype and Modulating the Maturation of Sertoli Cells

Cui, Lina; Gu, Yanli; Liu, Shuo; Li, Minghua; Ye, Jing; Zhang, Fanting; Luo, Xiaomin; Chang, Wen-Lin; Gui, Yaoting

doi:10.1007/s43032-020-00156-z

Cited by 8 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The blood‐testis barrier formed by the interaction between Sertoli cells and surrounding structures is the basis for maintaining various signalling pathways, sperm morphology, and cell polarity during spermatogenesis (Cui et al, 2020). The disorder of BTB connective structure or the abnormal expression of related proteins can affect the proliferation and differentiation of spermatogenic cells.…”

Section: Discussionmentioning

confidence: 99%

Cordycepin, a major bioactive component ofCordyceps militaris, ameliorates diabetes‐induced testicular damage through the Sirt1/Foxo3a pathway

Huang

Zhou

et al. 2021

Andrologia

View full text Add to dashboard Cite

Diabetes‐induced male dysfunction is considered as a worldwide challenge, and testicular damage mainly caused by oxidative stress is its most common manifestation. Cordycepin, a natural antioxidant, has been used in the treatment of diabetic complications. However, the protective action and underlying mechanism of cordycepin on hyperglycaemia‐induced testicular damage are unclear. This study aimed to investigate the protective effects and molecular mechanisms of cordycepin against diabetes‐induced testicular damage. The type 2 diabetes model was established in C57BL/6 male mice via high‐fat diet for 4 weeks and injected intraperitoneally with 50 mg/kg/day streptozotocin for five consecutive days. Then mice were treated with cordycepin (10 and 20 mg/kg, respectively) for 8 weeks. At the end of experiment, biochemical indicators, microstructure of testicular tissue, sperm morphology, TUNEL staining and protein expressions were evaluated. In the present study, cordycepin alleviated the testicular damage, restored disruption of the blood‐testis barrier, and improved spermatogenic function via the antiapoptotic and antioxidant capacity. Mechanistically, cordycepin significantly enhanced SIRT1 expression and triggered the activity of Foxo3a, further to induce the expression of its downstream antioxidant enzymes, including Mn‐SOD and CAT. These findings indicated that cordycepin could improve hyperglycaemia‐induced testicular damage by regulating downstream antioxidant enzymes activity through the SIRT1/Foxo3a signalling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Cordycepin, a major bioactive component ofCordyceps militaris, ameliorates diabetes‐induced testicular damage through the Sirt1/Foxo3a pathway

Huang

Zhou

et al. 2021

Andrologia

View full text Add to dashboard Cite

show abstract

“…Western blot analysis revealed a reduction of ~73% in the expression of SAT2 protein in the Sat2‐ MO group compared with that in the normal and control cohorts (Figure 1b,c). The testicular explants in the normal, control, and MO groups were cultured for 2 days and analyzed further by immunostaining for markers of Sertoli cells (SOX9) and germ cells (DDX4; Cui et al, 2020; Lee et al, 2018). Sat2 ‐MO treatment did not affect the number of Sertoli cells but, rather, led to the mislocation of Sertoli cells (Figure 1d,e).…”

Section: Resultsmentioning

confidence: 99%

“…Sertoli cells lacking kindlin‐2 (a key integrin‐binding protein) cause severe developmental defects in germ cells and destroy the integrity of blood–testis barrier (BTB) structures via regulation of the Hippo pathway in male mice (Chi et al, 2021). The loss of function of TBC1 domain family member 20 blocks Sertoli cell maturation and impairs BTB integrity, which mediates infertility in male mice (Cui et al, 2020). These studies provide evidence for the importance of Sertoli cell‐mediated gap junctions in testicular development and male fertility.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

SAT2 regulates Sertoli cell–germline interactions via STIM1‐mediated ROS/WNT/β‐catenin signaling pathway

Chen

Zheng

Han

et al. 2022

Cell Biology International

View full text Add to dashboard Cite

As the main component of seminiferous tubules, Sertoli cells are in close contact with germ cells and generate niche signals, which exhibit pivotal functions in spermatogenesis and male fertility. However, the regulatory mechanisms of Sertoli cell–germline interactions (SGIs) in the testes of neonatal mice (NM) remain largely unclear. Previously, we identified spermidine/spermine N1‐acetyl transferase 2 (SAT2) and stromal interaction molecule 1 (STIM1) to be potential regulators of testicular cord formation via comparative proteomics analysis. Here, we demonstrated a novel role of SAT2 for SGIs during testicular development in NM. Testicular explants lacking SAT2 affected the mislocation, but not the quantity, of Sertoli cells, which led to maintenance defects in spermatogonial stem cells (SSCs). Interestingly, SAT2 was essential for the migration of TM4 cells, a Sertoli cell line. Mechanistically, SAT2 was able to bind STIM1, repress its expression, and regulate homeostasis of a reactive oxygen species/wingless type (WNT)/β‐catenin pathway in NM testes. Collectively, our study identified that SAT2 was able to regulate SGIs via a STIM1‐mediated WNT signaling pathway.

show abstract

“…A causative gene mutation of the TBC1 domain family member 20 (TBC1D20) is response for the abnormal of phenotype of bs mice, which is characterized by congenital cataracts and male infertility [14,15]. Our previous study also found that TBC1D20 is essential for maintaining the integrity of the blood-testis barrier postnatally and viability of Sertoli cells by modulating the structure and function of the endoplasmic reticulum and Golgi apparatus [16,17]. Furthermore, during the breeding of bs mice, we also realized the phenomena of reducing reproductive capacity of female mouse with TBC1D20 deficiency.…”

Section: Introductionmentioning

confidence: 98%

TBC1D20 is Essential for Postnatal Uterine Development and Endometrial Decidualization in Mice

Min,

Li,

Zhou

et al. 2024

Clin. Exp. Obstet. Gynecol.

View full text Add to dashboard Cite

TBC1D20 Is Essential for Mouse Blood–Testis Barrier Integrity Through Maintaining the Epithelial Phenotype and Modulating the Maturation of Sertoli Cells

Cited by 8 publications

References 46 publications

Cordycepin, a major bioactive component ofCordyceps militaris, ameliorates diabetes‐induced testicular damage through the Sirt1/Foxo3a pathway

Cordycepin, a major bioactive component ofCordyceps militaris, ameliorates diabetes‐induced testicular damage through the Sirt1/Foxo3a pathway

SAT2 regulates Sertoli cell–germline interactions via STIM1‐mediated ROS/WNT/β‐catenin signaling pathway

TBC1D20 is Essential for Postnatal Uterine Development and Endometrial Decidualization in Mice

Contact Info

Product

Resources

About