Redox Regulation to Modulate Phosphorylation Events in Human Spermatozoa

Significance: Spermatozoa are complex and compartmentalized cells that undergo capacitation, a series of biochemical and morphological changes to acquire the ability to fertilize oocytes. Reactive oxygen species (ROS) have a prominent dual role in capacitation. At physiological levels, ROS regulate numerous cellular processes, including increases of cyclic adenosine monophosphate, calcium, and activation of phosphorylation events needed for capacitation. On the contrary, at high concentrations that do not impair sperm viability, ROS can cause loss of motility and inhibition of capacitation. Higher ROS concentrations promote oxidation of lipids, proteins, and DNA leading to cell death, and these damages have been associated with male infertility. Critical Issues: When incubated under specific conditions, spermatozoa can produce low and controlled amounts of ROS that are not harmful but instead regulate numerous cellular processes, including the phosphorylation of tyrosine, serine, and threonine residues in critical proteins needed for sperm capacitation. Here, we outline the complex redox signaling in human spermatozoa needed to achieve fertility and the role of ROS as physiological mediators that trigger phosphorylation cascades. Moreover, we illustrate the importance of various phosphoproteins in spermatozoa capacitation, viability, and hyperactive motility. Future Directions: Further studies to elucidate the different phosphorylation players during sperm capacitation and acrosome reaction (the regulated exocytotic event that releases proteolytic enzymes allowing the spermatozoon to penetrate the zona pellucida and fertilize the oocyte) are essential to understand how the spermatozoon acquires the fertilizing ability to fertilize the oocyte. This knowledge will serve to develop novel diagnostic tools and therapy for male infertility. Antioxid. Redox Signal. 37, 437–450.