Redox regulation of mammalian sperm capacitation.
Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS) that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P) H for sperm capacitation. Peroxiredoxins (PRDXs) are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.
Urology Research Laboratory, Surgery Department (Urology Division), Faculty of Medicine, McGill University; The Research Institute, McGill University Health Centre, Montréal, Québec, Canada.
Cristian
C
O'Flaherty
D000818:Animals; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics / Q000502:physiology*; D013075:Sperm Capacitation / Q000235:genetics / Q000502:physiology*; D013094:Spermatozoa / Q000201:enzymology; D013438:Sulfhydryl Compounds / Q000378:metabolism
D013438:Sulfhydryl Compounds; D010088:Oxidoreductases; D054464:Peroxiredoxins