Reactive oxygen species (ROS) are needed for the spermatozoon to promote hyperactivation, capacitation and ultimate acrosome reaction to be able to fertilize a mature oocyte1;2. Although it is clear that ROS are requirements for these processess, it is not well understood how the spermatozoon controls their production and action. This control is essential as we know that high levels of ROS generate sperm damage including DNA oxidation and fragmentation, loss of motility, inability to unergo capacitation, low sperm chromatin quality and subfertility3-6.
We recently characterized the Peroxiredoxin (PRDX) family of antioxidant enzymes in human and mouse spermatozoa. They are fully functional and they are considered the major protection against oxidative stress4-7. Peroxiredoxins are SH-dependent, selenium- and heme-free peroxidases that can reduce a variety of ROS including both organic and inorganic hydroperoxides, and ONOO-. They are readily oxidized and inactivated when cells are exposed even to low H2O2 levels. The six PRDXs isoforms are differentially localized, but present in all, sub-cellular compartments of human spermatozoa (nucleus, acrosome, cytoplasm, midpiece and flagellum), suggesting a local role in the control of ROS concentrations4;5;7. Spermatozoa from infertile men reduced amounts and inactivation of PRDXs along with sperm DNA damage and lower motility, suggesting an important role of these enzymes in the protection of spermatozoa against oxidative stress3. Prdx6-/- mice also showed oxidative stress-related damage in their spermatozoa and they are subfertile6. Inhibitors of 2-cys PRDXs and of PRDX6 prevented sperm capacitation in human and mouse, thus suggesting a regulatory role of PRDXs during mammalian sperm capacitation. In conclusion, PRDXs are major players in the antioxidant protection and regulation of redox signaling in mammalian spermatozoa and their deficiency and/or inactivation is associated with male infertility.