RESUMO
Varicocele (VCL) has been shown to induce severe oxidative stress in the testicular tissue resulting in 35% of males with primary infertility. To compare the exacerbating impacts of varicose on oxidative DNA damage and homeostatic antioxidant reactions in the seminiferous tubules (ST), enclosed and far from varicose vessels. Thirty mature Wistar rats were divided into control and VCL-induced groups. To approve VCL, the testicular diameters, volume, and blood circulation were measured using B-mode and Doppler ultrasonography. Next, to confirm oxidative stress (OS), the global homeostatic antioxidant biomarkers were evaluated. Moreover, the OS-induced oxidative DNA damage and homeostatic antioxidant reactions were compared between STs nearby and far from varicose vessels. Finally, to clarify the DNA damage-induced impact on the cell cycle progression, the global and local expressions of Cyclin D1, Cdk4, and p21 were examined. The VCL-induced group exhibited diminished global antioxidant status (marked with TAC, GPX, SOD, and CAT) and UNG and MPG expression levels. Moreover, the cross-sections of the VCL group represented a prominent reduction in the UNG, MPG, Cyclin D1, and cdk4, and upregulation in the p21 expression levels, more prominently in the STs nearby varicose vessels. Concerning severe oxidative DNA damage and intensive molecular changes in the STs nearby the varicose vessels, they can be considered the main cause of oxidative DNA damage in enclosed tubules. Thus, the varicose-mediated oxidative DNA damage negatively impacts the cell cycle progression in the tubules more intensively in the subcapsular area.
Assuntos
Antioxidantes , Varicocele , Ratos , Masculino , Humanos , Animais , Antioxidantes/farmacologia , Varicocele/metabolismo , Ciclina D1/metabolismo , Ratos Wistar , Testículo/metabolismo , Estresse Oxidativo , Túbulos Seminíferos/metabolismo , Pontos de Checagem do Ciclo CelularRESUMO
BACKGROUND: Uncontrolled type 1 diabetes mellitus (T1D) impairs reproductive potential of males. Insulin treatment restores metabolic parameters but it is unclear how it protects male reproductive health. Herein, we hypothesized that insulin treatment to T1D rats protects testicular physiology by mediating mechanisms associated with apoptosis and cell cycle. METHODS: Mature male Wistar rats (n = 24) were divided into 3 groups: control, T1D-induced (received 40 mg kg-1 streptozotocin) and insulin-treated T1D (Ins T1D; received 40 mg kg-1 streptozotocin and then treated 0.9 IU/100 gr of insulin for 56 days) (N = 8/group). Expression levels of intrinsic apoptosis pathways regulators (Bcl-2, Bax, Caspase-3 and p53) and core regulators of cell cycle machinery (Cyclin D1, Cdk-4 and p21) were determined in testicular tissue by immunohistochemistry (IHC) and RT-PCR techniques. The percentage of testicular apoptotic cells was evaluated by TUNEL staining. RESULTS: Our data shows that insulin treatment to T1D rats restored (P < 0.05) T1D-induced increased of caspase-3 and p53 expression in testis. Moreover, the testis of T1D rats treated with insulin exhibited increased expression of Cyclin D1 and cdk-4, and a reduced expression of p21 when compared with the expression in testis of T1D rats. Finally, insulin treatment could fairly control T1D-induced apoptosis. Accordingly, treatment of T1D rats with insulin led to a remarkable reduction (p < 0.05) in the percentage of apoptotic cells in the testis. CONCLUSIONS: Insulin treatment is able to restore the network expression of apoptosis and proliferation-related genes caused by T1D in the testis and via this mechanism, preserve the fertility of males.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/fisiologia , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Fertilidade , Expressão Gênica/efeitos dos fármacos , Masculino , Substâncias Protetoras/farmacologia , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Testículo/patologia , Testosterona/sangueRESUMO
PURPOSE: This study aimed to investigate the protective effects of isolated and co-administration of vitamin E (VitE) and dexamethasone (DEX) on varicocele (VCL)-induced damages in testicular tissue. MATERIALS AND METHODS: Wistar rats were divided into five groups (n=6), including; control-sham, non-treated VCL-induced, VitE-treated VCL-induced (VitE, 150 mg/kg, orally), DEX-administrated VCL-induced (DEX, 0.125 mg/kg, i.p.), VitE+DEX-received VCL-induced animals. The antioxidant status analyses, histopathological examinations, hormonal assay and tissue levels of alkaline phosphatase (ALP) were analyzed. The germinal epithelium RNA damage and Leydig cells steroidogenesis were analyzed. Moreover, the Hsp70-2 protein expression was examined based on immunohistochemical and western blot analyses. The sperm parameters, DNA integrity and chromatin condensation were investigated. RESULTS: VitE and DEX in simultaneous form of administration significantly (P<0.05) down-regulated the tissue ALP level and attenuated the VCL-decreased GSH-px, SOD and TAC levels and remarkably (P<0.05) down-regulated the testicular malondialdehyde (MDA) and nitric oxide (NO) contents. The VCL-induced histopathological alterations significantly (P<0.05) improved in VitE and DEX-administrated animals. The VitE and DEX co-administration reduced the VCL-increased RNA damage and elevated the Leydig cells steroidogenic activity. The Hsp70-2 protein level completely (P<0.05) increased in VitE and DEX alone-and-simultaneous-administrated animals. Finally, the VitE and DEX could significantly (P<0.05) improve the VCL-decreased semen quality and improved the sperm DNA integrity and chromatin condensation. CONCLUSION: Our data suggest that Vit E by up-regulating the antioxidant status and DEX by reducing inflammation-dependent oxidative and nitrosative stresses could improve the VCL-reduced Hsp70-2 chaperone expression and ultimately protected the testicular endocrine activities and promoted the spermatogenesis process.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Dexametasona/administração & dosagem , Proteínas de Choque Térmico HSP70/metabolismo , Varicocele/tratamento farmacológico , Vitamina E/administração & dosagem , Animais , Western Blotting , Cromatina/fisiologia , Dano ao DNA , Modelos Animais de Doenças , Interações Medicamentosas , Glutationa Peroxidase/análise , Imuno-Histoquímica , Masculino , Malondialdeído/análise , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Superóxido Dismutase/análise , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testículo/patologia , Testosterona/sangue , Varicocele/fisiopatologiaRESUMO
ABSTRACTPurpose:This study aimed to investigate the protective effects of isolated and co-administration of vitamin E (VitE) and dexamethasone (DEX) on varicocele (VCL)-induced damages in testicular tissue.Materials and Methods:Wistar rats were divided into five groups (n=6), including; control-sham, non-treated VCL-induced, VitE-treated VCL-induced (VitE, 150 mg/kg, orally), DEX-administrated VCL-induced (DEX, 0.125 mg/kg, i.p.), VitE+DEX-received VCL-induced animals. The antioxidant status analyses, histopathological examinations, hormonal assay and tissue levels of alkaline phosphatase (ALP) were analyzed. The germinal epithelium RNA damage and Leydig cells steroidogenesis were analyzed. Moreover, the Hsp70-2 protein expression was examined based on immunohistochemical and western blot analyses. The sperm parameters, DNA integrity and chromatin condensation were investigated.Results:VitE and DEX in simultaneous form of administration significantly (P<0.05) down-regulated the tissue ALP level and attenuated the VCL-decreased GSH-px, SOD and TAC levels and remarkably (P<0.05) down-regulated the testicular malondialdehyde (MDA) and nitric oxide (NO) contents. The VCL-induced histopathological alterations significantly (P<0.05) improved in VitE and DEX-administrated animals. The VitE and DEX co-administration reduced the VCL-increased RNA damage and elevated the Leydig cells steroidogenic activity. The Hsp70-2 protein level completely (P<0.05) increased in VitE and DEX alone–and-simultaneous-administrated animals. Finally, the VitE and DEX could significantly (P<0.05) improve the VCL-decreased semen quality and improved the sperm DNA integrity and chromatin condensation.Conclusion:Our data suggest that Vit E by up-regulating the antioxidant status and DEX by reducing inflammation-dependent oxidative and nitrosative stresses could improve the VCL-reduced Hsp70-2 chaperone expression and ultimately protected the testicular endocrine activities and promoted the spermatogenesis process.