High Cholesterol Content and Decreased Membrane Fluidity in Human Spermatozoa Are Associated With Protein Tyrosine Phosphorylation and Functional Deficiencies

Buffone, Mariano G.; Verstraeten, Sandra V.; Calamera, J.C.; Doncel, Gustavo F.

doi:10.2164/jandrol.108.006551

Cited by 55 publications

(46 citation statements)

References 32 publications

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“…Our current view of the in vivo situation is that the heterogeneous population of ejaculated sperm becomes exposed to mGX sPLA 2 (and possibly other sPLA 2 activities) after their mixing with seminal plasma secretions and/or during their swimming through the female tract. Indirect evidence supporting this view include the facts that (a) various populations of sperm with a different lipid composition, a damaged plasma membrane, and externalization of phosphatidylserine associated with spontaneous AR have been identified (13,14); (b) seminal plasma and female tract secretions contain endogenous PLA 2 regulators (26, 61-63); and …”

Section: Figurementioning

confidence: 99%

“…During capacitation, the most well-known modification of the plasma membrane is cholesterol efflux, which plays a major role in sperm maturation both in vivo and in vitro (5). Other major changes during capacitation include remodeling of lipid rafts, efflux of desmosterol, and changes in sterol sulfates, phospholipids, sphingomyelin, and ceramides, all of them likely contributing to the increase in membrane fluidity by changing lipid packing and thereby providing heterogeneity of the sperm population (5,(12)(13)(14). If several families of lipolytic enzymes are involved in these lipid modifications (15), phospholipases A 2 (PLA 2 s) are likely to be important, because of their abundant expression in male reproductive organs (16)(17)(18)(19) and because of their great diversity of action, from phospholipid remodeling and lipid mediator release to inflammation and host defense (20,21).…”

Section: Introductionmentioning

confidence: 99%

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Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice

Escoffier¹,

Jemel²,

Tanemoto³

et al. 2010

J. Clin. Invest.

100

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Ejaculated mammalian sperm must undergo a maturation process called capacitation before they are able to fertilize an egg. Several studies have suggested a role for members of the secreted phospholipase A 2 (sPLA 2 ) family in capacitation, acrosome reaction (AR), and fertilization, but the molecular nature of these enzymes and their specific roles have remained elusive. Here, we have demonstrated that mouse group X sPLA 2 (mGX) is the major enzyme present in the acrosome of spermatozoa and that it is released in an active form during capacitation through spontaneous AR. mGX-deficient male mice produced smaller litters than wild-type male siblings when crossed with mGX-deficient females. Further analysis revealed that spermatozoa from mGX-deficient mice exhibited lower rates of spontaneous AR and that this was associated with decreased in vitro fertilization (IVF) efficiency due to a drop in the fertilization potential of the sperm and an increased rate of aborted embryos. Treatment of sperm with sPLA 2 inhibitors and antibodies specific for mGX blocked spontaneous AR of wild-type sperm and reduced IVF success. Addition of lysophosphatidylcholine, a catalytic product of mGX, overcame these deficiencies. Finally, recombinant mGX triggered AR and improved IVF outcome. Taken together, our results highlight a paracrine role for mGX during capacitation in which the enzyme primes sperm for efficient fertilization and boosts premature AR of a likely phospholipid-damaged sperm subpopulation to eliminate suboptimal sperm from the pool available for fertilization.

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Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice

Escoffier¹,

Jemel²,

Tanemoto³

et al. 2010

J. Clin. Invest.

100

View full text Add to dashboard Cite

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“…13 Inhibitors of PKA block sperm capacitation and the associated increase in protein tyrosine phosphorylation. 42 Whatever the role of Tyr phosphorylation in capacitation, the level of Tyr phosphorylation in human sperm correlates strongly with the sperm-zona-binding capacity 43 and alterations in Tyr phosphorylation have been found in subfertile subjects 44 indicating its physiological role in fertilization.…”

mentioning

confidence: 99%

Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases

Ickowicz¹,

Finkelstein²,

Breitbart³

2012

Asian J Androl

204

130

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Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction (AR). The mechanisms of these modifications are not well characterized though protein kinases were shown to be involved in the regulation of intracellular Ca 21 during both capacitation and the AR. In the present review, we summarize some of the signaling events that are involved in capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase (PI3K) is phosphorylated/activated via a protein kinase A (PKA)-dependent cascade, and downregulated by protein kinase C a (PKCa). PKCa is active at the beginning of capacitation, resulting in PI3K inactivation. During capacitation, PKCa as well as PP1c2 is degraded by a PKA-dependent mechanism, allowing the activation of PI3K. The activation of PKA during capacitation depends mainly on cyclic adenosine monophosphate (cAMP) produced by the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads to an increase in actin polymerization, an essential process for the development of hyperactivated motility, which is necessary for successful fertilization. Actin polymerization is mediated by PIP 2 in two ways: first, PIP 2 acts as a cofactor for phospholipase D (PLD) activation, and second, as a molecule that binds and inhibits actin-severing proteins such as gelsolin. Tyrosine phosphorylation of gelsolin during capacitation by Src family kinase (SFK) is also important for its inactivation. Prior to the AR, gelsolin is released from PIP 2 and undergoes dephosphorylation/activation, resulting in fast F-actin depolymerization, leading to the AR.

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“…De plus, plusieurs études ont montré que certaines asthénozoosper-mies (absence ou faible mobilité des spermatozoïdes [47] (➜) sont associées chez l'homme à une composition lipidique défectueuse, caractérisée par un excès de cholestérol et de desmostérol, une faible concentration d'acide gras polyinsaturés (dont l'acide docosahexaénoïque) et une augmentation du contenu en acides gras saturés [21,22]. Ces résultats indiquent que la composition lipidique est un élément crucial pour un fonctionnement optimal du flagelle, et que toute altération des enzymes impliquées dans le contrôle de la composition lipidique de la membrane plasmique peut entraîner une asthénozoospermie chez l'homme [21,22] et la souris [23]. Cette diminution de la mobilité pourrait être liée à une altération de la fluidité membranaire, qui est très dépendante de la composition en lipides.…”

Section: Rôles Des Phospholipases Dans La Mobilité Spermatiqueunclassified

Les phospholipases, enzymes clés de la physiologie spermatique

et al. 2012

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> Chez les mammifères, la physiologie du spermatozoïde dans les voies génitales femelles est complexe, et plusieurs étapes bien définies doivent être franchies pour que le spermatozoïde puisse féconder l'ovocyte. Les phospholipases, qui permettent de contrôler la composition lipidique du spermatozoïde en hydrolysant les phospholipides de manière très spécifique, sont impliquées dans des mécanismes aussi variés que le contrôle du battement flagellaire, la capacitation, la réaction acrosomique, ainsi que dans le déclenchement des oscillations calciques de l'ovocyte qui entraînent l'activation ovocytaire. Deux phospholipases, la PLC et la PLA 2 sécrétée de groupe X, pourraient représenter des cibles thérapeutiques pour lutter contre l'infertilité masculine. < constituées d'une tête polaire phosphoalcoolique reliée, via une molécule de glycérol, à une queue hydrophobe constituée de deux acides gras [1]. Choline et éthanolamine sont les rési-dus alcool les plus courants au niveau de la partie polaire, mais d'autres, tels que la sérine ou l'inositol biphosphate, composent certaines GPL (Figure 1). Tous ces GPL sont hydrolysés par une superfamille de protéines, les phospholipases (PL). Les PL sont sépa-rées en quatre familles sans homologie structurale, sur la base de la localisation du site enzymatique d'hydrolyse :

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High Cholesterol Content and Decreased Membrane Fluidity in Human Spermatozoa Are Associated With Protein Tyrosine Phosphorylation and Functional Deficiencies

Cited by 55 publications

References 32 publications

Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice

Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice

Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases

Les phospholipases, enzymes clés de la physiologie spermatique

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