Hydrogen Sulfide As a Potential Target in Preventing Spermatogenic Failure and Testicular Dysfunction

Testis and sperm are particularly susceptible to inflammation and oxidative stress. Although hydrogen sulfide (H S) has been considered an important biological signaling molecule in inflammatory and oxidative stress processes, its role in the male reproductive system was poorly understood. The aim of this study was to investigate the role of H S in the regulation of male reproductive system. We found that both subfertile and infertile patients, especially asthenospermic patients, exhibited decreased concentration of H S in their seminal plasma and diminished expression of H S-generating enzyme (cystathionine β-synthase [CBS]) in sperm. Supplying exogenous H S to semen improved sperm motility of these asthenospermic patients. Furthermore, decreased sperm motility was observed in animal models with a defective in H S generation such as lipopolysaccharide-treated mice, diabetic mice, and CBS-deficient mice. Our research showed that stress-induced reductions of endogenous H S production and CBS expression are correlated with impaired spermatogenesis and a defective blood-testis barrier. Supplying exogenous H S or overexpressing CBS could relieve the spermatogenic failure. This occurred primarily through the combination of anti-inflammatory and antioxidative effects. These results provide the first indication that H S is important for maintaining male fertility and protecting testicular function. H S plays an important role in spermatogenic failure and testicular dysfunction mainly by its anti-inflammatory and antioxidative effects. Antioxid. Redox Signal. 28, 1447-1462.