mRNA-Expression von Angiopoietin 1 und 2 im ektopen Endometrium auf der Chorioallantoismembran (CAM)

In: Geburtshilfe und Frauenheilkunde · 2003 · vol. 63(12) , pp. 1279–1283 · doi:10.1055/s-2003-44651 · W2505718567
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This study investigated the mRNA expression of Angiopoietin 1 and 2 in ectopic endometrium on the chorioallantoic membrane as a model for endometriosis pathogenesis and angiogenesis.

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The study investigated implantation/angiogenesis of ectopic endometrium fragments using the chorioallantoic membrane (CAM) assay, comparing endometrium samples from patients with and without endometriosis (n = 15). After transplantation onto the CAM, the authors measured the time-course mRNA expression of angiopoietin (ANGPT) 1 and ANGPT2 and correlated these findings with a vessel density index as a readout of angiogenesis. ANGPT1 mRNA decreased after transplantation, while the ANGPT2/ANGPT1 ratio and CAM vessel density increased; endometrium from patients with and without endometriosis did not differ in ANGPT expression or the angiogenic response on the CAM. The paper concludes that angiogenesis is essential for implantation of ectopic endometrial fragments, while additional co-factors are likely involved. This paper is centrally about endometriosis — specifically, angiopoietin 1/2 expression and its relationship to angiogenesis during ectopic endometrium implantation in the CAM model.

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Abstract

Entscheidend für die Pathogenese der Endometriose ist der Implantationsprozess von ektopen Endometriumzellen an der Peritonealoberfläche. Den pathophysiologischen Mechanismus der Implantation stellt dabei die Angiogenese dar. Diese wird durch die Expression angiogenetisch relevanter Faktoren vermittelt, die in einem komplexen Ensemble zusammenwirken und sich gegenseitig beeinflussen. Das Expressionsverhältnis dieser Faktoren zueinander ergibt ein Abbild der angiogenetischen Aktivität; neben dem VEGF spielen dabei die Angiopoietine (ANGPT) eine richtungweisende Rolle.
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Material

und Methoden Wir untersuchten den Implantationsprozess von ektopen Endometriumfragmenten in einem dynamischen Modell der Endometriose, dem Chorioallantoismembran(CAM)-Modell. Nach Applikation auf die CAM wurde im Zeitverlauf die mRNA-Expression von ANGPT1 und 2 analysiert. Anhand der zeitgleichen Bestimmung des Gefäßdichteindexes der CAM konnten diese Ergebnisse mit der Angiogenese korreliert werden. Dabei wurden Endometriumproben von Patientinnen mit und ohne Endometriose verglichen (n = 15). Ergebnisse Es zeigte sich ein Anstieg der ANGPT2/ANGPT1-Ratio sowie eine signifikante Zunahme der Gefäßdichte auf der CAM. Endometriumproben von Patientinnen mit und ohne Endometriose unterschieden sich nicht hinsichtlich der untersuchten Parameter. Schlussfolgerung Die Angiogenese ist eine Voraussetzung für die Implantation von ektopem Endometrium und wird durch Expression angiogenetisch relevanter Faktoren vermittelt. Diese sind zugleich wichtige Parameter für die Aktivität der Endometriose. Für die Ausbildung von Endometriumläsionen sind jedoch noch weitere Faktoren einflussnehmend.

Abstract

Background The pathogenesis of endometriosis is dependent on implantation. Therefore, angiogenesis of the ectopic endometrium is discussed as a crucial step in the development of an endometriotic lesion. Angiogenesis is induced by the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) and angiopoietin (ANGPT) 1 and 2. These factors are important parameters for endometriosis.

Materials and methods

To investigate the implantation process of ectopic endometrium we used the chorioallantoic membrane (CAM) assay. We compared endometrium samples obtained from patients with and without endometriosis (n = 15). Post transplantation on the CAM we analysed the mRNA expression of ANGPT1 and ANGPT2 over time and correlated it to the angiogenetic reaction on the CAM by the vessel index.

Results

ANGPT1 mRNA expression decreased significantly after transplantation on the CAM. ANGPT2/ANGPT1 ratio increased as did the vessel index on the CAM. Endometrium samples of patients with and without endometriosis showed no differences either in mRNA expression of ANGPT1 and ANGPT2 or in induction of angiognesis on the CAM.

Conclusion

Angiogenesis is essential for the implantation of ectopic endometriotic fragments. Thus, angiogenic factors are important parameters for the activity of endometriosis. The establishment of an endometriotic lesion is influenced by other cofactors. Schlüsselwörter Endometriose - Angiogenese - VEGF - Angiopoietine - Aktivität - Implantation Key words Endometriosis - angiogenesis - VEGF - angiopoietin - activity - implantation Literatur - 1 Portuondo J A, Herrán C, Echanojauregui A D, Riego A G. Peritoneal flushing and biopsy in laparoscopically diagnosed endometriosis. Fertil Steril. 1982; 38 538-541 - 2 Ramney B. Etiology, prevention and inhibition of endometriosis. Clin Obstet Gynecol. 1980; 23 875-882 - 3 Ramzy I. Pathology. Schenken RS Endometriosis. Contemporary Concepts in Clinical Management. Philadelphia; Lippincott 1989: 49-81 - 4 Runnebaum B, Rabe T. Die Endometriose der Frau aus immunologischer und biologischer Sicht. 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Dorothee Maria Gescher Frauenklinik für Gynäkologie und Geburtshilfe Universitätsklinikum der RWTH Aachen Pauwelsstraße 30 52074 Aachen Email: [email protected]

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