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Title
Expression of angiogenetic factors in the eutopic endometrium in women with and without endometriosis and ectopic lesions / submitted by Gülen Yerlikaya
Additional Titles
Expression of angiogenetic factors in the eutopic endometrium in women with and without endometriosis and ectopic lesions
AuthorYerlikaya, Gülen
CensorStreubel, Berthold
PublishedWien, 2015
Edition
Elektronische Ressource
Descriptionxiv, 104 Blatt
Institutional NoteMedizinische Universität Wien, Dissertation, 2015
Annotation
Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüft
Abweichender Titel laut Übersetzung der Verfasserin/des Verfassers
LanguageEnglish
Bibl. ReferenceOeBB
Document typeDissertation (PhD)
Keywords (DE)Endometriose / Wachstumsfaktoren / Endometrium / Läsionen
URNurn:nbn:at:at-ubmuw:1-14989 Persistent Identifier (URN)
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 The work is publicly available
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Expression of angiogenetic factors in the eutopic endometrium in women with and without endometriosis and ectopic lesions [1.87 mb]
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Abstract (German)

Unter Endometriose versteht man das Vorkommen endometriumhaltiger Zellen außerhalb des Cavum uteri. Der genaue Entstehungsmechanismus ist noch nicht geklärt. Man geht von einem multifaktoriellen Geschehen aus, bei der die Angiogenese eine große Rolle spielt. Das Ziel dieser Arbeit war es, das Expressionsverhalten verschiedener Angiogenesefaktoren zu beschreiben. Folgende Faktoren wurden untersucht: VEGFA, VEGFR2, HIF1A,HGF,PDGFB, FGF 18, TNFa, TGFB2, EPO, ANG,EPHB4,NRP1.Ihr Expressionsmuster wurde bei gesunden und erkrankten Frauen, im eutopen Endometrium und im ektopem Gewebe verglichen. Ferner wurden unterschiedliche Gewebsproben der einen und derselben Patientin sowie das Expressionsmuster in unterschiedlichen ektopen Läsionen (Ovar, Peritoneum, Rektum) untersucht. Insgesamt wurden 205 Gewebsproben von 114 Frauen aufgearbeitet. Annährend alle Angiogenesefaktoren zeigten nennenswerte Anstiege im eutopen Endometrium bei Frauen mit Endometriose und 6 Faktoren (VEGFR2, HIF1A, HGF, PDGFB, NRP1 und EPHB4) im ektopen Läsionen im Vergleich zum Endometrium gesunder und kranker Frauen. Eine Hochregulation von VEGFR2, HIF1A und EPHB4 in eutopen Läsion konnte festgestellt werden. Für HIF1A, HGF und EPHB4 konnte keine significante hocregulation im Peritonealgewebe gezeigt werden, welches nicht direct von Endometriose betroffen war. Eine starke Korrellation wurde für drei Gene gefunden VEGFR2, PDGFB und EPHB4. Die Ergebnisse lassen den Schluss zu, dass unterschiedliche Angiogenesefaktoren bei der Entstehung der Endometriose beteiligt sind. Diese Faktoren sind unterschiedlich stark am Geschehen beteiligt und voneinander abhängig.

Abstract (English)

Endometriosis is one of the most common benign gynecological diseases in women of reproductive age. Endometriosis is a multifactorial event, in which angiogenesis plays a major role. Angiogenesis is a prerequisite for the formation of endometriotic lesions. In fact, the survival of endometriotic lesions depends on adequate blood supply. A number of angiogenetic factors have been investigated and reported on in literature, but there is little information about the interaction of these factors.The objective of the present study was to evaluate the expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia-inducible factor (HIF1A), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGFB), fibroblast growth factor 18 (FGF 18), tumor necrosis factor alpha (TNFa), transforming growth factor beta 2; (TGFB2), erythropoietin (EPO), angiogenin (ANG), ephrin receptor EphB4 (EPHB4), and neuropilin 1(NRP1), in the eutopic endometrium of women with and without endometriosis and ectopic lesions (in paired samples). The expression pattern of these factors with reference to the location of the ectopic lesion and gene expression in the peritoneum, which is not directly affected by endometriosis, were also investigated.Potential differences in the expression pattern with reference to cycle phases were studied, hormone therapies determined, and rAFS staging was performed. We also looked for a potential interrelationship between these factors, particularly with regard to the impact of VEGF. 205 tissue samples of 114 women were studied: 61 women with endometriosis and 53 without.151 endometriotic tissue samples, (including those from the eutopic and ectopic endometrium) and 54 peritoneal tissue samples were investigated. The samples were obtained during an operative laparoscopy. For detection and quantification of mRNA expression, each sample was analyzed by quantitative real-time PCR after RNA extraction. All samples revealed marked gene expression in the eutopic endometrium of women with endometriosis and ectopic lesions, in contrast to controls. No expression was registered for EPO or ANG in any of the three groups, and therefore all further investigation in regard of these entities was omitted. TNF[alpha] gene expression revealed no significant correlation in terms of tissue type or lesion location. We demonstrated that VEGFR2, HIF1A, HGF, PDGFB, NRP1 and EPHB4 were overexpressed in ectopic lesions compared to eutopic tissues of women with endometriosis. We further showed a significant upregulation of VEGFR2, HIF1A and EPHB4 in eutopic endometrial tissues of women with endometriosis compared to that of controls. Additionally, a significant downregulation for HIF1A, HGF and EPHB4 was observed in unaffected peritoneal tissues of women with endometriosis compared to controls. Interestingly, HIF1A, EPHB4 and HGF show an inverse expression in peritoneal tissues compared to eutopic endometrial tissues. Further, strong correlations were found between the three genes VEGFR2, PDGFB, and EPHB4.In light of the fact that not only VEGFA but also VEGFR2, HIF1A, PDGFB, NRP1 and EBHB4 are highly expressed in endometriotic implants, it is reasonable to speculate that beside VEGFA other angiogenic factors may play a crucial role in the progression of endometriosis or rather in angiogenesis and vascularization of endometrial implants. Our expression analysis of various angiogenetic factors has highlighted some new putative candidates regarding an association with endometriosis (EPHB4, PDGFB) and has confrimed already known candidates (VEGFA, VEGFR2, and HIF1A). Further studies should be performed to discover the exact role of these genes in the pathogenesis of endometriosis. ^In addition, a higher focus upon non-lesional, unaffected peritoneum of endometriosis patients seems beneficially in the context of endometriosis.

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