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Article: Zona pellucida-induced acrosome reaction in human spermatozoa is potentiated by glycodelin-A via down-regulation of extracellular signal-regulated kinases and up-regulation of zona pellucida-induced calcium influx

TitleZona pellucida-induced acrosome reaction in human spermatozoa is potentiated by glycodelin-A via down-regulation of extracellular signal-regulated kinases and up-regulation of zona pellucida-induced calcium influx
Authors
KeywordsERK
glycodelin
intracellular calcium
sperm acrosome reaction
zona pellucida
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/
Citation
Human Reproduction, 2010, v. 25 n. 11, p. 2721-2733 How to Cite?
Abstract
Background Glycodelin-A interacts with spermatozoa before fertilization, but its role in modulating sperm functions is not known. Zona pellucida-induced acrosome reaction is crucial to fertilization and its dysfunction is a cause of male infertility. We hypothesized that glycodelin-A, a glycoprotein found in the female reproductive tract, potentiates human spermatozoa for zona pellucida-induced acrosome reaction. Methods Glycodelin isoforms were immunoaffinity purified. The sperm intracellular cAMP concentration, protein kinase-A (PKA) and extracellular signal-regulated kinase (ERK) activities, and intracellular calcium were measured by ELISA, kinase activity assay kits and Fluo-4AM technique, respectively. The phosphorylation of inositol 1,4,5-trisphosphate type-1 receptor (IP3R1) mediated by ERK was determined by western blotting. Zona pellucida-induced acrosome reaction was detected by Pisum sativum staining. Results Pretreatment of spermatozoa with glycodelin-A significantly up-regulated adenylyl cyclase/PKA activity and down-regulated the activity of ERK and its phosphorylation of IP3R1, thereby enhancing zona pellucida-induced calcium influx and zona pellucida-induced acrosome reaction. Glycodelin-F or deglycosylated glycodelin-A did not have these actions. Treatment of spermatozoa with a protein kinase inhibitor abolished the priming activity of glycodelin-A, whilst ERK pathway inhibitors mimic the stimulatory effect of glycodelin-A on zona pellucida-induced acrosome reaction. Conclusions Glycodelin-A in the female reproductive tract sensitizes spermatozoa for zona pellucida-induced acrosome reaction in a glycosylation-specific manner through activation of the adenylyl cyclase/PKA pathway, suppression of extracellular signal-regulated kinase activation and up-regulation of zona pellucida-induced calcium influx. © 2010 The Author.
Descriptionpostprint
Persistent Identifierhttp://hdl.handle.net/10722/139900
ISSN
2013 Impact Factor: 4.585
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council, Hong KongHKU 7514/05M
HKU 7647/06M
Centre of Reproduction, Development and Growth, Academy of Finland
Helsinki University Central Hospital
Funding Information:

This work was supported by grants from the Research Grant Council, Hong Kong (HKU 7514/05M and HKU 7647/06M), Centre of Reproduction, Development and Growth, the Academy of Finland and the Helsinki University Central Hospital Research Fund.

References
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DC FieldValueLanguage
dc.contributor.authorChiu, PCNen_HK
dc.contributor.authorWong, BSTen_HK
dc.contributor.authorLee, CLen_HK
dc.contributor.authorLam, KKWen_HK
dc.contributor.authorChung, MKen_HK
dc.contributor.authorLee, KFen_HK
dc.contributor.authorKoistinen, Ren_HK
dc.contributor.authorKoistinen, Hen_HK
dc.contributor.authorGupta, SKen_HK
dc.contributor.authorSeppälä, Men_HK
dc.contributor.authorYeung, WSBen_HK
dc.date.accessioned2011-09-23T05:59:50Z-
dc.date.available2011-09-23T05:59:50Z-
dc.date.issued2010en_HK
dc.identifier.citationHuman Reproduction, 2010, v. 25 n. 11, p. 2721-2733en_HK
dc.identifier.issn0268-1161en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139900-
dc.descriptionpostprint-
dc.description.abstractBackground Glycodelin-A interacts with spermatozoa before fertilization, but its role in modulating sperm functions is not known. Zona pellucida-induced acrosome reaction is crucial to fertilization and its dysfunction is a cause of male infertility. We hypothesized that glycodelin-A, a glycoprotein found in the female reproductive tract, potentiates human spermatozoa for zona pellucida-induced acrosome reaction. Methods Glycodelin isoforms were immunoaffinity purified. The sperm intracellular cAMP concentration, protein kinase-A (PKA) and extracellular signal-regulated kinase (ERK) activities, and intracellular calcium were measured by ELISA, kinase activity assay kits and Fluo-4AM technique, respectively. The phosphorylation of inositol 1,4,5-trisphosphate type-1 receptor (IP3R1) mediated by ERK was determined by western blotting. Zona pellucida-induced acrosome reaction was detected by Pisum sativum staining. Results Pretreatment of spermatozoa with glycodelin-A significantly up-regulated adenylyl cyclase/PKA activity and down-regulated the activity of ERK and its phosphorylation of IP3R1, thereby enhancing zona pellucida-induced calcium influx and zona pellucida-induced acrosome reaction. Glycodelin-F or deglycosylated glycodelin-A did not have these actions. Treatment of spermatozoa with a protein kinase inhibitor abolished the priming activity of glycodelin-A, whilst ERK pathway inhibitors mimic the stimulatory effect of glycodelin-A on zona pellucida-induced acrosome reaction. Conclusions Glycodelin-A in the female reproductive tract sensitizes spermatozoa for zona pellucida-induced acrosome reaction in a glycosylation-specific manner through activation of the adenylyl cyclase/PKA pathway, suppression of extracellular signal-regulated kinase activation and up-regulation of zona pellucida-induced calcium influx. © 2010 The Author.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/en_HK
dc.relation.ispartofHuman Reproductionen_HK
dc.rightsThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Reproduction following peer review. The definitive publisher-authenticated version Human Reproduction, 2010, v. 25 n. 11, p. 2721-2733 is available online at: http://humrep.oxfordjournals.org/content/25/11/2721-
dc.subjectERKen_HK
dc.subjectglycodelinen_HK
dc.subjectintracellular calciumen_HK
dc.subjectsperm acrosome reactionen_HK
dc.subjectzona pellucidaen_HK
dc.subject.meshAcrosome Reaction - drug effects - physiology-
dc.subject.meshAdenylate Cyclase - metabolism-
dc.subject.meshCalcium - metabolism-
dc.subject.meshExtracellular Signal-Regulated MAP Kinases - metabolism-
dc.subject.meshGlycoproteins - physiology-
dc.titleZona pellucida-induced acrosome reaction in human spermatozoa is potentiated by glycodelin-A via down-regulation of extracellular signal-regulated kinases and up-regulation of zona pellucida-induced calcium influxen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0268-1161&volume=25&issue=11&spage=2721&epage=2733&date=2010&atitle=Zona+pellucida-induced+acrosome+reaction+in+human+spermatozoa+is+potentiated+by+glycodelin-A+via+down-regulation+of+extracellular+signal-regulated+kinases+and+up-regulation+of+zona+pellucida-induced+calcium+influx-
dc.identifier.emailChiu, PCN:pchiucn@hku.hken_HK
dc.identifier.emailLee, KF:ckflee@hku.hken_HK
dc.identifier.emailYeung, WSB:wsbyeung@hkucc.hku.hken_HK
dc.identifier.authorityChiu, PCN=rp00424en_HK
dc.identifier.authorityLee, KF=rp00458en_HK
dc.identifier.authorityYeung, WSB=rp00331en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/humrep/deq243en_HK
dc.identifier.pmid20843776en_HK
dc.identifier.scopuseid_2-s2.0-77958140629en_HK
dc.identifier.hkuros195594en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77958140629&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue11en_HK
dc.identifier.spage2721en_HK
dc.identifier.epage2733en_HK
dc.identifier.isiWOS:000283124000005-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectRole of olfactomedin in implantation-
dc.relation.projectThe mechanism of action of a novel glycodelin isoform from cumulus matrix on stimulating spermatozoa-zona pellucida binding-
dc.identifier.scopusauthoridChiu, PCN=25959969200en_HK
dc.identifier.scopusauthoridWong, BST=24337009700en_HK
dc.identifier.scopusauthoridLee, CL=9277221100en_HK
dc.identifier.scopusauthoridLam, KKW=25637362300en_HK
dc.identifier.scopusauthoridChung, MK=8964203600en_HK
dc.identifier.scopusauthoridLee, KF=26643097500en_HK
dc.identifier.scopusauthoridKoistinen, R=7006574669en_HK
dc.identifier.scopusauthoridKoistinen, H=7003612125en_HK
dc.identifier.scopusauthoridGupta, SK=23978174000en_HK
dc.identifier.scopusauthoridSeppälä, M=35475165300en_HK
dc.identifier.scopusauthoridYeung, WSB=7102370745en_HK
dc.identifier.citeulike7864113-

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