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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
Title | 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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Authors | |||||||||
Keywords | ERK glycodelin intracellular calcium sperm acrosome reaction zona pellucida | ||||||||
Issue Date | 2010 | ||||||||
Publisher | Oxford 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. | ||||||||
Persistent Identifier | http://hdl.handle.net/10722/139900 | ||||||||
ISSN | 2023 Impact Factor: 6.0 2023 SCImago Journal Rankings: 1.852 | ||||||||
ISI Accession Number ID |
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. | ||||||||
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DC Field | Value | Language |
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dc.contributor.author | Chiu, PCN | en_HK |
dc.contributor.author | Wong, BST | en_HK |
dc.contributor.author | Lee, CL | en_HK |
dc.contributor.author | Lam, KKW | en_HK |
dc.contributor.author | Chung, MK | en_HK |
dc.contributor.author | Lee, KF | en_HK |
dc.contributor.author | Koistinen, R | en_HK |
dc.contributor.author | Koistinen, H | en_HK |
dc.contributor.author | Gupta, SK | en_HK |
dc.contributor.author | Seppälä, M | en_HK |
dc.contributor.author | Yeung, WSB | en_HK |
dc.date.accessioned | 2011-09-23T05:59:50Z | - |
dc.date.available | 2011-09-23T05:59:50Z | - |
dc.date.issued | 2010 | en_HK |
dc.identifier.citation | Human Reproduction, 2010, v. 25 n. 11, p. 2721-2733 | en_HK |
dc.identifier.issn | 0268-1161 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/139900 | - |
dc.description.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. | en_HK |
dc.language | eng | en_US |
dc.publisher | Oxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/ | en_HK |
dc.relation.ispartof | Human Reproduction | en_HK |
dc.rights | This 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 | ERK | en_HK |
dc.subject | glycodelin | en_HK |
dc.subject | intracellular calcium | en_HK |
dc.subject | sperm acrosome reaction | en_HK |
dc.subject | zona pellucida | en_HK |
dc.subject.mesh | Acrosome Reaction - drug effects - physiology | - |
dc.subject.mesh | Adenylate Cyclase - metabolism | - |
dc.subject.mesh | Calcium - metabolism | - |
dc.subject.mesh | Extracellular Signal-Regulated MAP Kinases - metabolism | - |
dc.subject.mesh | Glycoproteins - physiology | - |
dc.title | 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 | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://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.email | Chiu, PCN:pchiucn@hku.hk | en_HK |
dc.identifier.email | Lee, KF:ckflee@hku.hk | en_HK |
dc.identifier.email | Yeung, WSB:wsbyeung@hkucc.hku.hk | en_HK |
dc.identifier.authority | Chiu, PCN=rp00424 | en_HK |
dc.identifier.authority | Lee, KF=rp00458 | en_HK |
dc.identifier.authority | Yeung, WSB=rp00331 | en_HK |
dc.description.nature | postprint | - |
dc.identifier.doi | 10.1093/humrep/deq243 | en_HK |
dc.identifier.pmid | 20843776 | - |
dc.identifier.scopus | eid_2-s2.0-77958140629 | en_HK |
dc.identifier.hkuros | 195594 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-77958140629&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 25 | en_HK |
dc.identifier.issue | 11 | en_HK |
dc.identifier.spage | 2721 | en_HK |
dc.identifier.epage | 2733 | en_HK |
dc.identifier.isi | WOS:000283124000005 | - |
dc.publisher.place | United Kingdom | en_HK |
dc.relation.project | Role of olfactomedin in implantation | - |
dc.relation.project | The mechanism of action of a novel glycodelin isoform from cumulus matrix on stimulating spermatozoa-zona pellucida binding | - |
dc.identifier.scopusauthorid | Chiu, PCN=25959969200 | en_HK |
dc.identifier.scopusauthorid | Wong, BST=24337009700 | en_HK |
dc.identifier.scopusauthorid | Lee, CL=9277221100 | en_HK |
dc.identifier.scopusauthorid | Lam, KKW=25637362300 | en_HK |
dc.identifier.scopusauthorid | Chung, MK=8964203600 | en_HK |
dc.identifier.scopusauthorid | Lee, KF=26643097500 | en_HK |
dc.identifier.scopusauthorid | Koistinen, R=7006574669 | en_HK |
dc.identifier.scopusauthorid | Koistinen, H=7003612125 | en_HK |
dc.identifier.scopusauthorid | Gupta, SK=23978174000 | en_HK |
dc.identifier.scopusauthorid | Seppälä, M=35475165300 | en_HK |
dc.identifier.scopusauthorid | Yeung, WSB=7102370745 | en_HK |
dc.identifier.citeulike | 7864113 | - |
dc.identifier.issnl | 0268-1161 | - |