4-hydroxy-2-nonenal and Infertility--Male

Oxidative stress has been long considered an important cause of male infertility, and sperm-derived reactive oxygen species (ROS) have been considered one of the major sources. In article number 1900205, Issue 2, Netherton et al. have improved upon current technologies for detection of true ROS-derived oxidative events from those originated by mitochondrial compounds. Moreover, the authors have isolated proteins that bear lipid aldehyde adducts, in order to verify their origin. In their paper, Netherton et al. demonstrate that sperm-derived ROS do not contribute to sperm oxidative stress, which is an important finding, given that most studies consider altered sperm a major source of seminal ROS. Moreover, adducted proteins are mostly of prostatic origin, which leads to questions regarding how and where the oxidative events occur. Under the light of this study and the methodological improvements it has brought, it may be important to revisit some foundation studies in semen and sperm oxidative stress.

Topics: Aldehydes; Humans; Infertility, Male; Male; Mass Spectrometry; Oxidative Stress; Reactive Oxygen Species; Semen; Sperm Motility; Spermatozoa; Superoxides

To assess the effect of seminal redox status on lipid peroxidation (LPO), apoptosis and integrity of sperm DNA in infertile males. Methods: In this case-control study, the total antioxidant status (TAS) and reactive oxygen species (ROS) levels were analyzed within the seminal plasma of fertile normozoospermic, n=40 and infertile (asthenozoospermic, n=30; oligoasthenoteratozoospermic, n=30) males. Additionally, the level of 4-hydroxynonenal (4-HNE), DNA fragmentation, and caspase-3 activity were estimated in the spermatozoa.. Significantly (p less than 0.001) increased seminal ROS level with decreased TAS scores was observed in the infertile groups compared to normozoospermics. The infertile males showed marked elevated (p less than 0.001) levels of 4-HNE, DNA fragmentation and caspase-3 activity compared to normozoospermics, which was positively correlated to increased seminal ROS levels and negatively to the TAS score in the studied groups. Seminal ROS level was significantly inverse correlated to the semen parameters. Additionally, a strong negative correlation between DNA fragmentation, LPO, caspase-3activity and seminal parameters were observed. Conclusion: Seminal oxidative stress is a potential risk factor for LPO, DNA damage, and apoptosis in spermatozoa, which can affect semen quality and male fertility. Thus, in addition to conventional seminological parameters, measurement of seminal oxidative stress and sperm DNA integrity may also be employed to investigate the functional integrity of spermatozoa at the molecular level.

Topics: Aldehydes; Antioxidants; Apoptosis; Caspase 3; DNA Fragmentation; Humans; Infertility, Male; Lipid Peroxidation; Male; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Risk Factors; Saudi Arabia; Semen; Spermatozoa

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