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Redox regulation of mammalian sperm capacitation.

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

Bottom Line: 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.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.

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

PRDXs regulate ROS signaling during human sperm capacitation. O2•–, H2O2, NO., and ONOO– are produced upon specific stimulation by capacitation inducers. 2-Cys PRDXs becomes oxidized and, therefore, inactive by reacting with H2O2. PRDX5 and PRDX6 react with either H2O2 or ONOO– and also become inactivated. This inactivation of PRDXs allows the rise of ROS in the different subcellular compartments of the spermatozoon to trigger the redox signaling necessary for capacitation. When the signal is delivered, PRDXs are reactivated by the thioredoxin–thioredoxin reductase system (for 2-Cys PRDXs and PRDX5) and by glutathione-S-transferases coupled to reduce GSH (for PRDX6). To accomplish the reactivation of PRDXs, it is necessary for a sufficient supply of NADPH (generated by G6PDH and by NAP-dependent ICDH) and of GSH. Failure to supply sufficient NADPH and GSH will reduce the ability to reactivate PRDXs and, therefore, permit the rise of ROS to toxic levels. ROS: reactive oxygen species; O2•–: superoxide anion; H2O2: hydrogen peroxide; NO•: nitric oxide; ONOO–: peroxynitrite; GSH: glutathione; G6PDH: glucose 6-phosphate dehydrogenase; ICDH: isocitrate dehydrogenase; PRDXs: peroxiredoxins.
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Figure 6: PRDXs regulate ROS signaling during human sperm capacitation. O2•–, H2O2, NO., and ONOO– are produced upon specific stimulation by capacitation inducers. 2-Cys PRDXs becomes oxidized and, therefore, inactive by reacting with H2O2. PRDX5 and PRDX6 react with either H2O2 or ONOO– and also become inactivated. This inactivation of PRDXs allows the rise of ROS in the different subcellular compartments of the spermatozoon to trigger the redox signaling necessary for capacitation. When the signal is delivered, PRDXs are reactivated by the thioredoxin–thioredoxin reductase system (for 2-Cys PRDXs and PRDX5) and by glutathione-S-transferases coupled to reduce GSH (for PRDX6). To accomplish the reactivation of PRDXs, it is necessary for a sufficient supply of NADPH (generated by G6PDH and by NAP-dependent ICDH) and of GSH. Failure to supply sufficient NADPH and GSH will reduce the ability to reactivate PRDXs and, therefore, permit the rise of ROS to toxic levels. ROS: reactive oxygen species; O2•–: superoxide anion; H2O2: hydrogen peroxide; NO•: nitric oxide; ONOO–: peroxynitrite; GSH: glutathione; G6PDH: glucose 6-phosphate dehydrogenase; ICDH: isocitrate dehydrogenase; PRDXs: peroxiredoxins.

Mentions: PRDX6 is the only family member with Ca2+-independent phospholipase A2 (Ca2+ iPLA2) activity.106 When we incubated spermatozoa under capacitating conditions in the presence of 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33), an inhibitor of the Ca2+ iPLA2 activity of PRDX6,108 we also observed a reduction in tyrosine phosphorylation to a level similar to those of noncapacitated spermatozoa (Figure 5). This experiment opens new avenues for research to elucidate the regulation of phospholipids and of restructuring of plasma membrane components during sperm capacitation. From these studies, we can hypothesize that 2-Cys PRDXs are needed to control the ROS produced during capacitation to assure the signaling required to make the spermatozoon competent to recognize and fertilize the oocyte (Figure 6). This is supported by the fact that low amounts and thiol oxidation of PRDXs are associated with men infertility.88


Redox regulation of mammalian sperm capacitation.

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

PRDXs regulate ROS signaling during human sperm capacitation. O2•–, H2O2, NO., and ONOO– are produced upon specific stimulation by capacitation inducers. 2-Cys PRDXs becomes oxidized and, therefore, inactive by reacting with H2O2. PRDX5 and PRDX6 react with either H2O2 or ONOO– and also become inactivated. This inactivation of PRDXs allows the rise of ROS in the different subcellular compartments of the spermatozoon to trigger the redox signaling necessary for capacitation. When the signal is delivered, PRDXs are reactivated by the thioredoxin–thioredoxin reductase system (for 2-Cys PRDXs and PRDX5) and by glutathione-S-transferases coupled to reduce GSH (for PRDX6). To accomplish the reactivation of PRDXs, it is necessary for a sufficient supply of NADPH (generated by G6PDH and by NAP-dependent ICDH) and of GSH. Failure to supply sufficient NADPH and GSH will reduce the ability to reactivate PRDXs and, therefore, permit the rise of ROS to toxic levels. ROS: reactive oxygen species; O2•–: superoxide anion; H2O2: hydrogen peroxide; NO•: nitric oxide; ONOO–: peroxynitrite; GSH: glutathione; G6PDH: glucose 6-phosphate dehydrogenase; ICDH: isocitrate dehydrogenase; PRDXs: peroxiredoxins.
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Related In: Results  -  Collection

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Figure 6: PRDXs regulate ROS signaling during human sperm capacitation. O2•–, H2O2, NO., and ONOO– are produced upon specific stimulation by capacitation inducers. 2-Cys PRDXs becomes oxidized and, therefore, inactive by reacting with H2O2. PRDX5 and PRDX6 react with either H2O2 or ONOO– and also become inactivated. This inactivation of PRDXs allows the rise of ROS in the different subcellular compartments of the spermatozoon to trigger the redox signaling necessary for capacitation. When the signal is delivered, PRDXs are reactivated by the thioredoxin–thioredoxin reductase system (for 2-Cys PRDXs and PRDX5) and by glutathione-S-transferases coupled to reduce GSH (for PRDX6). To accomplish the reactivation of PRDXs, it is necessary for a sufficient supply of NADPH (generated by G6PDH and by NAP-dependent ICDH) and of GSH. Failure to supply sufficient NADPH and GSH will reduce the ability to reactivate PRDXs and, therefore, permit the rise of ROS to toxic levels. ROS: reactive oxygen species; O2•–: superoxide anion; H2O2: hydrogen peroxide; NO•: nitric oxide; ONOO–: peroxynitrite; GSH: glutathione; G6PDH: glucose 6-phosphate dehydrogenase; ICDH: isocitrate dehydrogenase; PRDXs: peroxiredoxins.
Mentions: PRDX6 is the only family member with Ca2+-independent phospholipase A2 (Ca2+ iPLA2) activity.106 When we incubated spermatozoa under capacitating conditions in the presence of 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33), an inhibitor of the Ca2+ iPLA2 activity of PRDX6,108 we also observed a reduction in tyrosine phosphorylation to a level similar to those of noncapacitated spermatozoa (Figure 5). This experiment opens new avenues for research to elucidate the regulation of phospholipids and of restructuring of plasma membrane components during sperm capacitation. From these studies, we can hypothesize that 2-Cys PRDXs are needed to control the ROS produced during capacitation to assure the signaling required to make the spermatozoon competent to recognize and fertilize the oocyte (Figure 6). This is supported by the fact that low amounts and thiol oxidation of PRDXs are associated with men infertility.88

Bottom Line: 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.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.

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