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

Document Type : Original Article


1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

3 Isfahan Fertility and Infertility Centre, Isfahan, Iran


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 antioxidant
response by inducing the transcription of a wide array of genes that can combat the harmful effects of factors
such as oxidative stress. The purpose of this study was to evaluate the effect of N-acetyl-L-cysteine (NAC), as an
antioxidant 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 enzymes
were 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 compared
to pre-treatment status, whereas the percentage of abnormal morphology and DNA fragmentation was significantly
decreased (p <0.05). A significant improvement in expression of NRF 2 gene and antioxidant enzyme levels were observed
compared to pre-treatment by NAC (p <0.05). Significant correlations were observed between NRF 2 mRNA
expression 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 enhancing
NRF 2 expression. This could improve semen parameters quality parameters in asthenoteratozoospermia men (Registration
number: IRCT20170830035998N4).