Background Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury. Methods Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group. Conclusion BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。
Background: Although varicocele is considered to be one of the leading causes of male infertility, the precise mechanism underlying how varicocele leads to male infertility is not completely understood. We found the lactate concentration on the varicocele side of the patients was decreased compare with peripheral venous blood. In the testicles, the lactate produced by the sertoli cells (TM4) through the glycolysis pathway provides most of the energy needed for spermatogenesis, the reduction of lactate will affect spermatogenesis. The objective of this study was to investigate the mechanism of this abnormal energy metabolism phenomenon in varicocele.Methods: In this study, we collected the testicular tissue from patients with varicocele, the glycolysis related proteins PHGDH was identified by iTRAQ proteomics technology. Experimental rat varicocele model was constructed according to our new clip technique, the mRNA and protein expression levels of PHGDH were examined with qRT-PCR and Western blotting. We constructed a TM4 cell of PHGDH down-regulation model, and then detected the glucose consumption, LDH activities and lactate production in the TM4 cells. Western blot was conducted to investigate the effects of PHGDH on the expression of phosphoserine phosphatase (PSPH) and Pyruvate kinase M2 (PKM2). Flow cytometry was used to detect the cell apoptosis and cell cycle in TM4 cells.Results: The results showed that testicular protein PHGDH was down-regulated in varicocele. Down-regulation of PHGDH in TM4 cells significantly decreased the glucose consumption, LDH activities and lactate production in the TM4 cells, indicating that the low expression of PHGDH ultimately led to a decrease in lactate production by affecting the glycolysis. The Western blot results showed that the down-regulation of PHGDH significantly reduced the expression of pathway protein PSPH and PKM2, leading to the reduction of lactate production. Moreover, PHGDH knockdown can promote apoptosis and inhibit cell cycle to affect cell growth.Conclusions: Overall, we conformed that varicocele lead to the decreasing of testis lactate production. Down-regulation of PHGDH in TM4 cells may mediate the process of abnormal glucose metabolism. Our study provide new insight into the mechanisms underlying metabolism-associated male infertility and suggests a novel therapeutic target for male infertility.
This study investigates the therapeutic effect and the underlying mechanisms of ergothioneine (EGT) on the testicular damage caused by varicocele (VC) in vivo, in vitro, and in silico. This preclinical study combines a series of biological experiments and network pharmacology analyses. A total of 18 Sprague Dawley (SD) male rats were randomly and averagely divided into three groups: the sham-operated, VC model, and VC model with EGT treatment (VC + EGT) groups. The left renal vein of the VC model and the VC + EGT groups were half-ligated for 4 weeks. Meanwhile, the VC + EGT group was intragastrically administrated with EGT (10 mg/kg). GC1 and GC2 cells were exposed to H 2 O 2 with or without EGT treatment to re-verify the conclusion. The structure disorder of seminiferous tubules ameliorated the apoptosis decrease in the VC rats receiving EGT. EGT can also increase the sperm quality of the VC model rats (p < 0.05). The exposure to H 2 O 2 decreased proliferation and increased apoptosis of GC1 and GC2 cells, which was revisable by adding EGT to the plates (p < 0.05). The network pharmacology and molecular docking were conducted to explore the potential targets of EGT in VC, and HSP90AA1 was identified as the pivotal gene, which was validated by western blot, immunohistochemistry, and RT-qPCR both in vivo and in vitro (p < 0.05). Overall, EGT attenuates the testicular injury in the VC model both in vivo and in vitro by potentially potentiating the expression of HSP90AA1.
Background Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury. Methods Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group. Conclusion BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。
Background: Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury.Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group.Conclusion: BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。
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