4-hydroxy-2-nonenal and Varicocele

Oxidative stress is involved in male infertility. However, little is known about how it impairs spermatogenesis. We investigated the presence of oxidative stress in human testes by studying the generation of 4-hydroxy-2-nonenal modified proteins and expressions of proliferating cell nuclear antigen and p53.. A total of 47 testicular biopsies from patients with varicocele, obstructive azoospermia and idiopathic infertility were included. Localization and generation of 4-hydroxy-2-nonenal modified proteins were determined by immunohistochemistry and Western blotting. The expressions of proliferating cell nuclear antigen and p53 were assessed by Western blotting. The interaction between 4-hydroxy-2-nonenal modified proteins and p53 was examined by immunoprecipitation. Data were compared to clinicopathological parameters.. 4-Hydroxy-2-nonenal modified proteins were strongly positive in spermatogonia, primary spermatocytes and Sertoli's cells, and generation was inversely correlated with expression of proliferating cell nuclear antigen. The expression of p53 was increased in testes with varicocele (p <0.01) and obstructive azoospermia (p <0.05), and there was a positive or inverse correlation with 4-hydroxy-2-nonenal modified proteins and proliferating cell nuclear antigen. Immunoprecipitated p53 was detected by anti-4-hydroxy-2-nonenal modified protein antibody.. 4-Hydroxy-2-nonenal impairs the proliferation of germ cells through the up-regulation of p53 protein, especially in testes with varicocele. Modification by 4-hydroxy-2-nonenal might alter normal function and stabilization of p53 protein.

Topics: Adult; Aldehydes; Blotting, Western; Humans; Immunohistochemistry; Infertility, Male; Male; Oxidative Stress; Proliferating Cell Nuclear Antigen; Spermatogenesis; Testis; Tumor Suppressor Protein p53; Varicocele

Increasing evidence suggests that testes with varicocele are exposed to oxidative stress (OS) with deterioration in spermatogenesis; however, the relationship between testicular OS and outcome after varicocelectomy is poorly understood. Levels of testicular 4-hydroxy-2-nonenal modified proteins, an OS marker, were significantly higher in responders than in nonresponders, suggesting that varicocelectomy reduces OS in testis.

Topics: Adult; Aldehydes; Biomarkers; Humans; Infertility, Male; Male; Oxidative Stress; Proliferating Cell Nuclear Antigen; Proteins; Reproducibility of Results; Sensitivity and Specificity; Sperm Motility; Spermatogenesis; Testis; Treatment Outcome; Varicocele; Vascular Surgical Procedures

Oxidative stress is involved in the pathogenesis of testicular disorders. Haem oxygenase-1 (HO-1) plays an important cytoprotective role against oxidative stress. We investigated the presence of oxidative stress, represented by generation of 4-hydroxy-2-nonenal (4-HNE)-modified proteins, and expression of HO-1 in varicocele testes of human.. Thirty testicular biopsies from patients with left varicocele and 10 from patients with normal spermatogenesis were included. Generation of 4-HNE-modified proteins was examined as a marker of oxidative stress. Expression of HO-1 was assessed by western blotting and immunohistochemistry. The expression was compared with clinico-pathological parameters.. Increased generation of 4-HNE-modified proteins was observed in varicocele testes. HO-1 expression was significantly correlated with varicocele grade (P < 0.01 in grade 2 and 3 compared to control) and expression of 4-HNE-modified proteins (r = 0.508, P < 0.01). The immunoreactivity was increased in Leydig cells in varicocele testes. There were significant correlations between age, total motile sperm count, Johnsen's mean score and HO-1:4-HNE-modified protein ratio (r = 0.206, 0.405 and 0.408, P = 0.027, 0.027 and 0.025 respectively).. In testes with varicocele, there are increases in 4-HNE-modified proteins, suggesting that oxidative stress is present. Increased HO-1 expression, mainly in Leydig cells, is considered to protect the cells against oxidative stresses in varicocele testes.

Topics: Adult; Aldehydes; Biopsy; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Leydig Cells; Male; Membrane Proteins; Middle Aged; Oxidative Stress; Spermatogenesis; Varicocele