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Redox regulation of mammalian sperm capacitation.

O'Flaherty C - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon.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.

View Article: PubMed Central - PubMed

Affiliation: Urology Research Laboratory, Surgery Department (Urology Division), Faculty of Medicine, McGill University; The Research Institute, McGill University Health Centre, Montréal, Québec, Canada.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Production of ROS during mammalian sperm capacitation. Capacitation-associated production of ROS occurs on the plasma membrane of the spermatozoon. Still unrevealed a putative sperm oxidase produces O2•– that can dismutate spontaneously to form H2O2, triggering capacitation. SOD and CAT, both acting extracellularly, are able to block sperm capacitation, thus confirming that the production of these ROS forms is at the level of the plasma membrane. NO is also needed for sperm capacitation. Candidates for the source of this ROS could be a specific NOS or an oxidase with intrinsic NOS activity since L-NAME or L-NMMA–both inhibitors of NOS activity – prevent capacitation. It is also plausible that endogenous production of ROS is required for capacitation. AC: adenylyl cyclase; PTK: protein tyrosine kinase; ROS: reactive oxygen species; SOD: superoxide dismutase; NO: nitric oxide; CAT: catalase; H2O2: hydrogen peroxide; O2•–: superoxide anion; NOS: nitric oxide synthase.
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Figure 1: Production of ROS during mammalian sperm capacitation. Capacitation-associated production of ROS occurs on the plasma membrane of the spermatozoon. Still unrevealed a putative sperm oxidase produces O2•– that can dismutate spontaneously to form H2O2, triggering capacitation. SOD and CAT, both acting extracellularly, are able to block sperm capacitation, thus confirming that the production of these ROS forms is at the level of the plasma membrane. NO is also needed for sperm capacitation. Candidates for the source of this ROS could be a specific NOS or an oxidase with intrinsic NOS activity since L-NAME or L-NMMA–both inhibitors of NOS activity – prevent capacitation. It is also plausible that endogenous production of ROS is required for capacitation. AC: adenylyl cyclase; PTK: protein tyrosine kinase; ROS: reactive oxygen species; SOD: superoxide dismutase; NO: nitric oxide; CAT: catalase; H2O2: hydrogen peroxide; O2•–: superoxide anion; NOS: nitric oxide synthase.

Mentions: Capacitation-associated ROS production must occur at the plasma membrane level in human and bull spermatozoa because capacitation was prevented by the addition of SOD or CAT to the incubation medium (Figure 1).85354 These antioxidant enzymes act outside the spermatozoon, removing the ROS generated upon stimulation with capacitation inducers in both species.85354 Noteworthy, ROS production by human spermatozoa stimulated with NADPH cannot be prevented by mitochondrial inhibitors such as antimycin A, rotenone or carbonyl cyanide m-chlorophenylhydrazone.55 From these studies, it is clear that the sperm oxidase resides in the plasma membrane and is unlikely that the mitochondria are the source of ROS for capacitation.


Redox regulation of mammalian sperm capacitation.

O'Flaherty C - Asian J. Androl. (2015 Jul-Aug)

Production of ROS during mammalian sperm capacitation. Capacitation-associated production of ROS occurs on the plasma membrane of the spermatozoon. Still unrevealed a putative sperm oxidase produces O2•– that can dismutate spontaneously to form H2O2, triggering capacitation. SOD and CAT, both acting extracellularly, are able to block sperm capacitation, thus confirming that the production of these ROS forms is at the level of the plasma membrane. NO is also needed for sperm capacitation. Candidates for the source of this ROS could be a specific NOS or an oxidase with intrinsic NOS activity since L-NAME or L-NMMA–both inhibitors of NOS activity – prevent capacitation. It is also plausible that endogenous production of ROS is required for capacitation. AC: adenylyl cyclase; PTK: protein tyrosine kinase; ROS: reactive oxygen species; SOD: superoxide dismutase; NO: nitric oxide; CAT: catalase; H2O2: hydrogen peroxide; O2•–: superoxide anion; NOS: nitric oxide synthase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492048&req=5

Figure 1: Production of ROS during mammalian sperm capacitation. Capacitation-associated production of ROS occurs on the plasma membrane of the spermatozoon. Still unrevealed a putative sperm oxidase produces O2•– that can dismutate spontaneously to form H2O2, triggering capacitation. SOD and CAT, both acting extracellularly, are able to block sperm capacitation, thus confirming that the production of these ROS forms is at the level of the plasma membrane. NO is also needed for sperm capacitation. Candidates for the source of this ROS could be a specific NOS or an oxidase with intrinsic NOS activity since L-NAME or L-NMMA–both inhibitors of NOS activity – prevent capacitation. It is also plausible that endogenous production of ROS is required for capacitation. AC: adenylyl cyclase; PTK: protein tyrosine kinase; ROS: reactive oxygen species; SOD: superoxide dismutase; NO: nitric oxide; CAT: catalase; H2O2: hydrogen peroxide; O2•–: superoxide anion; NOS: nitric oxide synthase.
Mentions: Capacitation-associated ROS production must occur at the plasma membrane level in human and bull spermatozoa because capacitation was prevented by the addition of SOD or CAT to the incubation medium (Figure 1).85354 These antioxidant enzymes act outside the spermatozoon, removing the ROS generated upon stimulation with capacitation inducers in both species.85354 Noteworthy, ROS production by human spermatozoa stimulated with NADPH cannot be prevented by mitochondrial inhibitors such as antimycin A, rotenone or carbonyl cyanide m-chlorophenylhydrazone.55 From these studies, it is clear that the sperm oxidase resides in the plasma membrane and is unlikely that the mitochondria are the source of ROS for capacitation.

Bottom Line: Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon.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.

View Article: PubMed Central - PubMed

Affiliation: Urology Research Laboratory, Surgery Department (Urology Division), Faculty of Medicine, McGill University; The Research Institute, McGill University Health Centre, Montréal, Québec, Canada.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus