Redox regulation of mammalian sperm capacitation

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.

The achievement of boar spermin vitrocapacitation is related to an increase of disrupted disulphide bonds and intracellular reactive oxygen species levels

“…While this moderate increase appeared to have no deleterious effects, it could be, as previously suggested (O'Flaherty, 2015), related to the achievement of sperm capacitation. While this moderate increase appeared to have no deleterious effects, it could be, as previously suggested (O'Flaherty, 2015), related to the achievement of sperm capacitation.…”

“…The effects of GSH on ROS were of lesser extent than those observed in free cysteine residues and the increase of intracellular ROS following incubation of spermatozoa in CM was moderate. While this moderate increase appeared to have no deleterious effects, it could be, as previously suggested (O'Flaherty, 2015), related to the achievement of sperm capacitation. In this regard, it is worth noting that moderate changes in intracellular ROS levels modulate the activity of protein kinases and phosphatases that are involved in sperm capacitation (e.g.…”

Reactive oxygen species as mediators of sperm capacitation and pathological damage

“…The mechanisms by which ROS stimulate sperm capacitation are numerous, and involve the stimulation of adenylyl cyclase activity (Aitken et al, ; Lewis & Aitken, ; Rivlin et al, ; Zhang & Zheng, ), accompanied by the activation of protein kinase A (O'Flaherty, de Lamirande, & Gagnon, ,b); the induction of cholesterol oxidation and consequent efflux from the plasma membrane (Boerke et al, ); the activation of Extracellular signal regulated kinase‐like proteins (O'Flaherty et al, ,); and the inhibition of tyrosine phosphatase activity (Hecht and Zick, ). In vivo, capacitation is also associated with increased thiol abundance on certain proteins (O'Flaherty, ) on the sperm surface, where the thiols may trigger the release of fully capacitated cells from their resting place on the surface of the oviductal epithelium (Gualtieri, Mollo, Duma, & Talevi, ). Such increases in thiol abundance were previously reported to be a consequence of oxidative stress (Kralikova et al, ), and may reflect a defensive response mediated by a capacitation‐dependent increase in nicotinamide adenine dinucleotide phosphate (NADPH) generation fuelled by the hexose monophosphate shunt (Urner & Sakkas, ).…”

An evolutionary conserved interaction between the Gcm transcription factor and the SF1 nuclear receptor in the female reproductive system

“…Capacitation is primordial for fertilisation and spermatozoids are viable in the female reproductive tract for several days in human5, several years in honey bees67 and several decades in ants8. In both mammals and insects, the inability to capacitate/store the spermatozoids has a strong impact on female fertility9101112131415.…”