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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

Participation of isoforms of LDH-C4 during bull sperm capacitation induced by NADH in vitro. The LDH-C4pm located at the plasma membrane utilizes exogenous pyruvate and NADH to produce lactate and NAD+. Lactate will then enter into the spermatozoon and be converted into pyruvate and NADH by the LDHcyt as described in Figure 2. Cytosolic oxidases can then utilize the NADH to generate cytosolic O2•– needed for capacitation. ROS: reactive oxygen species; LDH-C4pm: lactate dehydrogenase-C4; O2•– superoxide anion.
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Figure 3: Participation of isoforms of LDH-C4 during bull sperm capacitation induced by NADH in vitro. The LDH-C4pm located at the plasma membrane utilizes exogenous pyruvate and NADH to produce lactate and NAD+. Lactate will then enter into the spermatozoon and be converted into pyruvate and NADH by the LDHcyt as described in Figure 2. Cytosolic oxidases can then utilize the NADH to generate cytosolic O2•– needed for capacitation. ROS: reactive oxygen species; LDH-C4pm: lactate dehydrogenase-C4; O2•– superoxide anion.

Mentions: Although the extracellular production of O2•– necessary for sperm capacitation is well-documented in different mammalian species,678910 it is possible that other oxidases might exist in the spermatozoon and be involved in capacitation. The incubation of bull or human spermatozoa with NADH promotes capacitation without involving extracellular production of O2•–.6571 The existence of a LDH-C4 in the plasma membrane of bull spermatozoa65 suggests that extracellular NADH added to the medium can be used along with pyruvate (already present in the medium) by this enzyme to produce lactate that will diffuse into the cytosol and be used by cytosolic oxidases that will generate O2•– and/or H2O2 to stimulate targets on the plasma membrane (e.g., AC) or in the cytosol (e.g., kinases) to promote capacitation (Figure 3).


Redox regulation of mammalian sperm capacitation.

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

Participation of isoforms of LDH-C4 during bull sperm capacitation induced by NADH in vitro. The LDH-C4pm located at the plasma membrane utilizes exogenous pyruvate and NADH to produce lactate and NAD+. Lactate will then enter into the spermatozoon and be converted into pyruvate and NADH by the LDHcyt as described in Figure 2. Cytosolic oxidases can then utilize the NADH to generate cytosolic O2•– needed for capacitation. ROS: reactive oxygen species; LDH-C4pm: lactate dehydrogenase-C4; O2•– superoxide anion.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Participation of isoforms of LDH-C4 during bull sperm capacitation induced by NADH in vitro. The LDH-C4pm located at the plasma membrane utilizes exogenous pyruvate and NADH to produce lactate and NAD+. Lactate will then enter into the spermatozoon and be converted into pyruvate and NADH by the LDHcyt as described in Figure 2. Cytosolic oxidases can then utilize the NADH to generate cytosolic O2•– needed for capacitation. ROS: reactive oxygen species; LDH-C4pm: lactate dehydrogenase-C4; O2•– superoxide anion.
Mentions: Although the extracellular production of O2•– necessary for sperm capacitation is well-documented in different mammalian species,678910 it is possible that other oxidases might exist in the spermatozoon and be involved in capacitation. The incubation of bull or human spermatozoa with NADH promotes capacitation without involving extracellular production of O2•–.6571 The existence of a LDH-C4 in the plasma membrane of bull spermatozoa65 suggests that extracellular NADH added to the medium can be used along with pyruvate (already present in the medium) by this enzyme to produce lactate that will diffuse into the cytosol and be used by cytosolic oxidases that will generate O2•– and/or H2O2 to stimulate targets on the plasma membrane (e.g., AC) or in the cytosol (e.g., kinases) to promote capacitation (Figure 3).

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