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Conference Paper: Glycodelin-a suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activities

TitleGlycodelin-a suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activities
Authors
KeywordsGlycodelin
Trophoblast
Invasion
Urokinase plasminogen activator
Extracellular signal regulated kinase
Issue Date2010
PublisherESHRE.
Citation
The 26th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE 2010), Rome, Italy, 27-30 June 2010. How to Cite?
AbstractINTRODUCTION: Invasion of the extravillous cytotrophoblast into the maternal endometrium is crucial to placenta formation and is strictly regulated by paracrine and autocrine interactions. Dysregulation of the process results in a wide spectrum of abnormal pregnancies, like preeclampsia, choriocarcinoma and intrauterine growth restriction. One of the invasive phenotypes of extravillous cytotrophoblast is production of matrix degrading enzyme, including urokinase plasminogen activator (uPA). Extracellular signal regulated kinase (ERK), a member of the mitogen activated protein kinase (MAPK) family is known to control trophoblast invasion and migration. Glycodelin-A (GdA), a glycoprotein abundantly synthesized by the decidua but not the trophoblast, is upregulated during first trimester coinciding with the time of trophoblast invasion. We hypothesize that decidual-derived glycodelin-A is a paracrine regulator fine-tuning the invasion of human trophoblast. MATERIAL & METHODS: Trans-well invasion assay was used to examine the effect of GdA and MEK (MAPK kinase) inhibitors (PD98059 & U0126) on the invasiveness of an immortalized first trimester extravillous cytotrophoblast (TEV-1) and a choricarcinoma (JEG-3) cell line. The RNA expression, proteinase activity and secretion of uPA were determined by real time quantitative PCR, quantitative urokinase activity assay and ELISA, respectively. Western blotting analysis was employed to examine the effect of GdA on ERK activities. RESULTS: Transwell invasion assay showed that GdA, but not deglycosylated GdA, significantly reduced the invasiveness of the cells. At 30 pmol/ml, it inhibited 47.7±8.7% of TEV-1 and 27.1±4.7% of JEG-3 invasion. The suppressive effect of GdA on invasion was associated with a suppression of uPA proteinase activity. The transcription and secretion of uPA were also significantly reduced by 72.0±4.3% and 36.13±8.8% respectively after GdA (30 pmol/ml) treatment. Western blotting analysis showed that GdA suppressed the phosphorylated ERK level in a dose dependent manner. The involvement of ERK in the trophoblast invasion was supported by the observation that MEK inhibitors PD98059 and U0126 that reduced phosphorylation of ERK also significantly suppressed the invasiveness of trophoblast. A dose-dependent down-regulation of uPA mRNA was also noted by the real time quantitative PCR after treatment with these inhibitors at concentrations that did not affect cell viability. CONCLUSIONS: This is the first report demonstrating a suppression of trophoblast invasion and uPA transcription through down regulating ERK activities in trophoblast cell lines. Thus, GdA is a potential paracrine regulator at the fetal-maternal interface limiting the extent of trophoblast invasion. The results may have implication in pregnancy complications such as preeclampsia, which is characterized by shallow invasion. Consistently, trophoblast cells from preeclamptic women have reduced uPA proteolytic activities.
DescriptionPoster Session - Early pregnancy. Abstract: P-132
Persistent Identifierhttp://hdl.handle.net/10722/142980

 

DC FieldValueLanguage
dc.contributor.authorLam, KKWen_US
dc.contributor.authorChiu, PCNen_US
dc.contributor.authorLee, CLen_US
dc.contributor.authorYeung, WSBen_US
dc.contributor.authorHo, PCen_US
dc.date.accessioned2011-10-28T03:00:47Z-
dc.date.available2011-10-28T03:00:47Z-
dc.date.issued2010en_US
dc.identifier.citationThe 26th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE 2010), Rome, Italy, 27-30 June 2010.en_US
dc.identifier.urihttp://hdl.handle.net/10722/142980-
dc.descriptionPoster Session - Early pregnancy. Abstract: P-132-
dc.description.abstractINTRODUCTION: Invasion of the extravillous cytotrophoblast into the maternal endometrium is crucial to placenta formation and is strictly regulated by paracrine and autocrine interactions. Dysregulation of the process results in a wide spectrum of abnormal pregnancies, like preeclampsia, choriocarcinoma and intrauterine growth restriction. One of the invasive phenotypes of extravillous cytotrophoblast is production of matrix degrading enzyme, including urokinase plasminogen activator (uPA). Extracellular signal regulated kinase (ERK), a member of the mitogen activated protein kinase (MAPK) family is known to control trophoblast invasion and migration. Glycodelin-A (GdA), a glycoprotein abundantly synthesized by the decidua but not the trophoblast, is upregulated during first trimester coinciding with the time of trophoblast invasion. We hypothesize that decidual-derived glycodelin-A is a paracrine regulator fine-tuning the invasion of human trophoblast. MATERIAL & METHODS: Trans-well invasion assay was used to examine the effect of GdA and MEK (MAPK kinase) inhibitors (PD98059 & U0126) on the invasiveness of an immortalized first trimester extravillous cytotrophoblast (TEV-1) and a choricarcinoma (JEG-3) cell line. The RNA expression, proteinase activity and secretion of uPA were determined by real time quantitative PCR, quantitative urokinase activity assay and ELISA, respectively. Western blotting analysis was employed to examine the effect of GdA on ERK activities. RESULTS: Transwell invasion assay showed that GdA, but not deglycosylated GdA, significantly reduced the invasiveness of the cells. At 30 pmol/ml, it inhibited 47.7±8.7% of TEV-1 and 27.1±4.7% of JEG-3 invasion. The suppressive effect of GdA on invasion was associated with a suppression of uPA proteinase activity. The transcription and secretion of uPA were also significantly reduced by 72.0±4.3% and 36.13±8.8% respectively after GdA (30 pmol/ml) treatment. Western blotting analysis showed that GdA suppressed the phosphorylated ERK level in a dose dependent manner. The involvement of ERK in the trophoblast invasion was supported by the observation that MEK inhibitors PD98059 and U0126 that reduced phosphorylation of ERK also significantly suppressed the invasiveness of trophoblast. A dose-dependent down-regulation of uPA mRNA was also noted by the real time quantitative PCR after treatment with these inhibitors at concentrations that did not affect cell viability. CONCLUSIONS: This is the first report demonstrating a suppression of trophoblast invasion and uPA transcription through down regulating ERK activities in trophoblast cell lines. Thus, GdA is a potential paracrine regulator at the fetal-maternal interface limiting the extent of trophoblast invasion. The results may have implication in pregnancy complications such as preeclampsia, which is characterized by shallow invasion. Consistently, trophoblast cells from preeclamptic women have reduced uPA proteolytic activities.-
dc.languageengen_US
dc.publisherESHRE.en_US
dc.relation.ispartofAnnual Meeting of the European Society of Human Reproduction and Embryology, ESHRE 2010-
dc.subjectGlycodelin-
dc.subjectTrophoblast-
dc.subjectInvasion-
dc.subjectUrokinase plasminogen activator-
dc.subjectExtracellular signal regulated kinase-
dc.titleGlycodelin-a suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activitiesen_US
dc.typeConference_Paperen_US
dc.identifier.emailLam, KKW: h0327370@HKUSUA.hku.hken_US
dc.identifier.emailChiu, PCN: pchiucn@hku.hken_US
dc.identifier.emailLee, CL: kcllee@hku.hken_US
dc.identifier.emailYeung, WSB: wsbyeung@hkucc.hku.hken_US
dc.identifier.emailHo, PC: pcho@hkusub.hku.hk-
dc.identifier.authorityChiu, PCN=rp00424en_US
dc.identifier.authorityYeung, WSB=rp00331en_US
dc.identifier.authorityHo, PC=rp00325en_US
dc.identifier.hkuros184338en_US
dc.description.otherThe 26th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE ROME 2010), Rome, Italy, 27-30 June 2010.-

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