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

Abstract

Superoxide dismutase (SOD) is a ubiquitous antioxidant enzyme that catalytically converts the superoxide radical to hydrogen peroxide (H2O2). 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 Caenorhabditis elegans, sod-1 and sod-2, 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 sod-1;sod-2 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 sod-1;sod-2 mutant sperm. Surprisingly, H2O2, the dismutation product of SOD, could activate sod-1;sod-2 mutant sperm treated with Pronase. Moreover, the H2O2 scavenger ebselen completely inhibited pseudopod extension in wild-type sperm treated with Pronase, and H2O2 could directly induce pseudopod extension in wild-type sperm. Analysis of Pronase-triggered sperm activation in sod-1 and sod-2 single mutants revealed that sod-2 is required for pseudopod extension. These results suggest that SOD-2 plays an important role in the sperm activation of C. elegans by producing H2O2 as an activator of pseudopod extension.