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

Document Type : Original Article

Authors

1 Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

2 Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

3 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

4 Medical Biology Research Center, Health Technology Institute, Kermanshah University of MedicalSciences, Kermanshah, Iran

5 Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

6 Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA

Abstract

Background: Reactive oxygen species (ROS) play a crucial role in etiology of DNA fragmentation and lipid peroxidation
in sperm, leading to infertility in men. The silent information regulators SIRT1 and SIRT3 are members of the
sirtuins protein family known to be involved in cancer genetics, aging and oxidative stress responses. The aim ofthis
study is to determine the correlation between SIRT1 and SIRT3 with antioxidants, oxidative stress biomarkers, and
DNA fragmentation in the semen of asthenoteratozoospermic and normozoospermic men.

Materials and Methods: In this case-control study, after spermogram analysis the specimens were divided into
two 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.Catalase
activity was measured using the Aebi spectrophotometeric method. Total antioxidant capacity (TAC) level and superoxide
dismutase (SOD) activitywere measured by using commercially available colorimetric assays. Enzyme-linked
immune 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 in
comparison with the normozoospermic group (p <0.001).The percentage of DNA fragmentation and MDA level in the
asthenoteratozoospermic group were remarkably higher than in the normozoospermic group. The SIRT1 and SIRT3
protein levels in seminal plasmawere remarkably lower in asthenoteratozoospermic group than the normozoospermic
group (p <0.001).

Conclusion: The results of this study suggest that SIRT1 and SIRT3 protein levels are negatively correlated with
oxidative stress and DNA fragmentation in semen. The low levels of SIRT1 and SIRT3 in asthenoteratozoospermic
men may lead to an increase in oxidative stress, DNA fragmentation, and lipid peroxidation that eventually result in
immotile and immature spermatozoa (asthenoteratozoospermia).

Keywords


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