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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
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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
 
AuthorsChiu, PCN1 1
Wong, BST1
Lee, CL1
Lam, KKW1
Chung, MK3
Lee, KF1 1
Koistinen, R4
Koistinen, H4
Gupta, SK2
Seppälä, M4
Yeung, WSB1 1
 
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/
 
CitationHuman Reproduction, 2010, v. 25 n. 11, p. 2721-2733 [How to Cite?]
DOI: http://dx.doi.org/10.1093/humrep/deq243
 
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.
 
Descriptionpostprint
 
ISSN0268-1161
2012 Impact Factor: 4.67
2012 SCImago Journal Rankings: 2.172
 
DOIhttp://dx.doi.org/10.1093/humrep/deq243
 
ISI Accession Number IDWOS:000283124000005
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.

 
ReferencesReferences in Scopus
 
GrantsRole of olfactomedin in implantation
The mechanism of action of a novel glycodelin isoform from cumulus matrix on stimulating spermatozoa-zona pellucida binding
 
DC FieldValue
dc.contributor.authorChiu, PCN
 
dc.contributor.authorWong, BST
 
dc.contributor.authorLee, CL
 
dc.contributor.authorLam, KKW
 
dc.contributor.authorChung, MK
 
dc.contributor.authorLee, KF
 
dc.contributor.authorKoistinen, R
 
dc.contributor.authorKoistinen, H
 
dc.contributor.authorGupta, SK
 
dc.contributor.authorSeppälä, M
 
dc.contributor.authorYeung, WSB
 
dc.date.accessioned2011-09-23T05:59:50Z
 
dc.date.available2011-09-23T05:59:50Z
 
dc.date.issued2010
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.descriptionpostprint
 
dc.identifier.citationHuman Reproduction, 2010, v. 25 n. 11, p. 2721-2733 [How to Cite?]
DOI: http://dx.doi.org/10.1093/humrep/deq243
 
dc.identifier.citeulike7864113
 
dc.identifier.doihttp://dx.doi.org/10.1093/humrep/deq243
 
dc.identifier.epage2733
 
dc.identifier.hkuros195594
 
dc.identifier.isiWOS:000283124000005
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.

 
dc.identifier.issn0268-1161
2012 Impact Factor: 4.67
2012 SCImago Journal Rankings: 2.172
 
dc.identifier.issue11
 
dc.identifier.openurl
 
dc.identifier.pmid20843776
 
dc.identifier.scopuseid_2-s2.0-77958140629
 
dc.identifier.spage2721
 
dc.identifier.urihttp://hdl.handle.net/10722/139900
 
dc.identifier.volume25
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofHuman Reproduction
 
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.relation.referencesReferences in Scopus
 
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.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.subjectERK
 
dc.subjectglycodelin
 
dc.subjectintracellular calcium
 
dc.subjectsperm acrosome reaction
 
dc.subjectzona pellucida
 
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 influx
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. National Institute of Immunology India
  3. Chinese University of Hong Kong
  4. Helsinki University Central Hospital