The Influence of Varicocele and Microsurgical Varicocelectomy on Semen Quality, as Determined by Metabolic Analysis

The influence of varicocele and microsurgical varicocelectomy on semen quality remains unclear. No previous study has investigated the relationship between semen metabolism and the abnormalities in reproductive function caused by varicocele. Here, we used the non-targeted and targeted metabolic analysis to investigate the different metabolites in seminal plasma within normal, varicocele, and varicocelectomy groups. We clearly showed that varicocele significantly affects sperm metabolism, and microsurgical varicocelectomy can reverse this metabolic abnormality. Moreover, we characterized the landscape of three dipeptides in the seminal plasma of patients with varicocele that have not been identified previously in human tissues or biofluids. Interestingly, the levels of these three dipeptides decreased after microsurgical varicocelectomy coincident with an improvement in semen quality. Western blotting confirmed the downregulation of DPEP3 (dipeptidase 3) in the varicocele group and the upregulation of DPEP3 in the varicocelectomy group. Furthermore, we found that eight metabolites may be helpful to distinguish varicocele patients from normal subjects. Our results can be applied to earlier diagnosis or to predict the outcome of microsurgery for varicocele.