Hydrogen peroxide produced by superoxide dismutase SOD-2 activates sperm in .

Superoxide dismutase (SOD) is a ubiquitous antioxidant enzyme that catalytically converts the superoxide radical to hydrogen peroxide (HO). In mammals, high SOD activity is detectable in sperm and seminal plasma, and loss of SOD activity has been correlated with male infertility; however, the underlying mechanisms of sperm infertility remain to be clarified. Here we report that the deletion of two major SOD genes in , and , causes sperm activation defects, leading to a significant reduction in brood size. By examining the reactivity to the sperm activation signals Pronase and triethanolamine, we found that ; double mutant sperm cells display defects in pseudopod extension. Neither the content nor oxidative modification of major sperm protein, an essential cytoskeletal component for crawling movement, were significantly affected in ; mutant sperm. Surprisingly, HO, the dismutation product of SOD, could activate mutant sperm treated with Pronase. Moreover, the HO scavenger ebselen completely inhibited pseudopod extension in wild-type sperm treated with Pronase, and HO could directly induce pseudopod extension in wild-type sperm. Analysis of Pronase-triggered sperm activation in and single mutants revealed that is required for pseudopod extension. These results suggest that SOD-2 plays an important role in the sperm activation of by producing HO as an activator of pseudopod extension.