Introduction: Male factor is responsible for about half of infertility problems. However, the reasons for the decrease in male fertility are still broadly unclear. The mechanisms of how smoking may impact male fertility have not been established. However, with its influence on different semen parameters, it is regarded as a risk factor for infertility.
Aim: To investigate the effect of chronic smoking on spermatozoa NRF2 expression and DNA fragmentation in infertile men with apparently normal seminogram and to determine if NRF2 expression and DNA fragmentation markers could be possible predictors of the impact of chronic cigarette smoking on male fertility.
Methods: Semen samples were collected from 170 subjects; 65 nonsmokers (40 fertile and 25 infertile) and 105 smokers (25 fertile and 80 infertile). NRF2 gene expression, 8-OHdG and DNA fragmentation were assayed.
Results: There were significant increases in 8-OHdG and %DNA fragmentation with a significant decrease in NRF2 gene expression in infertile smokers. ROC curve analysis of spermatozoa NRF2 gene expression showed 95% sensitivity 93.3% specificity at cutoff value ≤0. 931 (p <0.0001) differentiating infertile smokers from controls. Moreover, seminal 8-OHdG assay shows 93.4% sensitivity, 89.2% % specificity, at cutoff values >19.33 pg/ml predicting the detrimental effect of smoking on spermatozoa DNA.
Conclusion: Chronic cigarette smoking may be a hidden causative mechanism of delayed fertility. Spermatozoa NRF2 gene expression and seminal 8-OHdG levels may serve as sensitive diagnostic indicators predicting smoking induced infertility. So, the presence of normal seminal parameters could not be an exclusion of potential effect of chronic smoking on male fertility.