Enhancing Expression of NRF2 Antioxidant Gene by NAC Supplementation in Infertile Men

Background: Reactive oxygen species (ROS) play an impor-tant role in male infertility. Nuclear factor erythroid 2-related factor 2 (NRF2) can up-regulate the expression of antioxidant genes and protect cells from oxidative damage. The current study suggests that effect of N-acetyl-cysteine on sperm qual-ity in asthenoteratozoospermia men is associated closely with NRF2 gene expression.Materials and Methods: The study was carried out in the unit of ACECR Infertility Research Center, Qom, Iran. The patients consisted of 50 infertile men with asthenoteratozoospermia, who received NAC (600 mg/d) orally for 3 months, after which they were compared with pre-treatment status. Semen was ana-lyzed according to WHO (2010) for DNA integrity [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)]. Quantitative real-time reverse transcriptase poly-merase chain reaction was used for detecting the level of NRF2 mRNA expression in ejaculated spermatozoa. Seminal plasma levels of antioxidant enzymes were determined by ELISA kit. Results: After NAC treatment, patients sperm concentration and motility increased significantly whereas abnormal mor-phology and DNA fragmentation showed significant decreases compared to pre-treatment levels (P<0.05). NAC treatment sig-nificantly increased seminal plasma of antioxidant enzyme lev-els compared with baseline values (P<0.05). Furthermore, NAC treatment significantly unregulated NRF2 levels in sperm in comparison to untreated NAC (P<0.05).Significant correlations were observed between the level of NRF2 mRNA expression, specific sperm parameters and levels of antioxidant enzymes (P<0.05).Conclusion: The results demonstrate that NAC oral supple-mentation protects against oxidative stress by activating the Nrf2 antioxidant defense system and improving sperm param-eters in infertile men.

کلیدواژه ها:

Nuclear Related Factor 2 ، N-Acetyl-Cysteine ، Oxida-tive Stress ، Asthenoteratozoospermia