Evaluation of The Relationship among The Levels of SIRT1 and SIRT3 with Oxidative Stress and DNA Fragmentation in Asthenoteratozoospermic Men

Abstract

Background: Reactive oxygen species (ROS) play a crucial role in etiology of DNA fragmentation and lipid peroxidationin sperm, leading to infertility in men. The silent information regulators SIRT1 and SIRT3 are members of thesirtuins protein family known to be involved in cancer genetics, aging and oxidative stress responses. The aim ofthisstudy is to determine the correlation between SIRT1 and SIRT3 with antioxidants, oxidative stress biomarkers, andDNA fragmentation in the semen of asthenoteratozoospermic and normozoospermic men.Materials and Methods: In this case-control study, after spermogram analysis the specimens were divided intotwo groups, normozospermic (n=40) and asthenoteratozoospermic (n=40), according to World Health Organization(WHO) standards. Sperm DNA fragmentation was evaluatedusing the sperm chromatin dispersion (SCD) test.Catalaseactivity was measured using the Aebi spectrophotometeric method. Total antioxidant capacity (TAC) level and superoxidedismutase (SOD) activitywere measured by using commercially available colorimetric assays. Enzyme-linkedimmune sorbent assay (ELISA) was used to measure SIRT1 and SIRT3 protein levels of seminal plasma. Malondialdehyde(MDA) level in seminal plasma was determined by high-performance liquid chromatography (HPLC).Results: The asthenoteratozoospermic group had significantly lower catalase and SOD activities and TAC levels incomparison with the normozoospermic group (p <0.001).The percentage of DNA fragmentation and MDA level in theasthenoteratozoospermic group were remarkably higher than in the normozoospermic group. The SIRT1 and SIRT3protein levels in seminal plasmawere remarkably lower in asthenoteratozoospermic group than the normozoospermicgroup (p <0.001).Conclusion: The results of this study suggest that SIRT1 and SIRT3 protein levels are negatively correlated withoxidative stress and DNA fragmentation in semen. The low levels of SIRT1 and SIRT3 in asthenoteratozoospermicmen may lead to an increase in oxidative stress, DNA fragmentation, and lipid peroxidation that eventually result inimmotile and immature spermatozoa (asthenoteratozoospermia).

Keywords

• dna fragmentation
• infertility
• oxidative stress
• sirt1
• sirt3