Regulation of sperm function by reactive oxygen species.

Sperm capacitation can be increased by the addition of reactive oxygen species (ROS) and decreased by antioxidants. Broadly consistent results have been achieved with a wide variety of methods and across different species. Exposure to ROS increases protein tyrosine phosphorylation consequent on an increase in cAMP and activation of tyrosine kinase and inhibition of tyrosine phosphatase. The measurement of ROS production by sperm is complicated by contamination of suspensions by leukocytes, laying many studies open to doubt. In human sperm the observation that extracellular NADPH could support superoxide production detected with the chemiluminescent probe lucigenin and had physiological effects similar to hydrogen peroxide led to the suggestion that they contained NADPH oxidase activity to generate ROS to support capacitation. However, the realization that lucigenin can signal superoxide artefactually, combined with failure to detect superoxide production using spin trapping techniques or to detect NADPH oxidase components in mature sperm, and confirmation of old reports that NADPH solution contains substantial amounts of hydrogen peroxide due to autoxidation, have undermined this hypothesis. Although the presence of significant NADPH oxidase activity in mature human sperm now seems less likely, other observations continue to suggest that they can make ROS in some way. There is stronger evidence that animal sperm can make ROS although these may be mainly of mitochondrial origin.