The Effect of N-Acetyl-Cysteine on NRF 2 Antioxidant Gene Expression in Asthenoteratozoospermia Men: A Clinical Trial Study

Abstract

Background: One of the important factor associated with male infertility is high production of reactive oxygen species(ROS). The main function of Nuclear factor erythroid 2-related factor 2 (NRF 2) is to activate the cellular antioxidantresponse by inducing the transcription of a wide array of genes that can combat the harmful effects of factorssuch as oxidative stress. The purpose of this study was to evaluate the effect of N-acetyl-L-cysteine (NAC), as anantioxidant drug, on NRF 2 Gene Expression in Asthenoteratozoospermia Men.Materials and Methods: In this randomized, blinded clinical trial study, included 50 infertile men with asthenoteratozoospermia,who received NAC (600 mg, three times daily). Sperm parameters analyzed according to the world health organization(WHO; 2010). Sperm DNA fragmentation, relative NRF 2 expression, and seminal plasma level of antioxidant enzymeswere measured by TUNEL assay, reverse transcription polymerase chain reaction (RT-PCR) and ELISA test, respectively.Results: After NAC treatment, findings showed a significant increase in sperm concentration and motility comparedto pre-treatment status, whereas the percentage of abnormal morphology and DNA fragmentation was significantlydecreased (p <0.05). A significant improvement in expression of NRF 2 gene and antioxidant enzyme levels were observedcompared to pre-treatment by NAC (p <0.05). Significant correlations were observed between NRF 2 mRNAexpression level, specific sperm parameters and level of antioxidant enzymes (p <0.05).Conclusion: The results demonstrated that NAC oral supplementation protected against oxidative stress by enhancingNRF 2 expression. This could improve semen parameters quality parameters in asthenoteratozoospermia men (Registrationnumber: IRCT20170830035998N4).

Keywords

• factor erythroid 2-related factor 2
• nuclear asthenoteratozoospermia
• n-acetyl-cysteine
• oxidative stress