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Hum. Reprod. Advance Access published online on December 3, 2004
Human Reproduction, doi:10.1093/humrep/deh571
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Human Reproduction © European Society of Human Reproduction and Embryology 2004; all rights reserved
Received April 6, 2004
Revised September 20, 2004
Accepted September 29, 2004

Article

mRNA analysis of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis using a real-time quantitative RT-PCR assay

L. Ramón 1, J. Gilabert-Estellés 2, R. Castelló 1, J. Gilabert 3, F. España 1, A. Romeu 1, M. Chirivella 4, J. Aznar 5, and A. Estellés 1*

1 Research Center, Hospital Universitario La Fe, Valencia, Spain
2 Maternal Hospital, Hospital Universitario La Fe, Valencia, Spain
3 Gynecology Service, Hospital Arnau de Vilanova, Valencia, Spain
4 Anatomopathology, Hospital Universitario La Fe, Valencia, Spain
5 Clinical Pathology Departments, Hospital Universitario La Fe, Valencia, Spain

* To whom correspondence should be addressed.
A. Estellés, E-mail: estelles_amp{at}gva.es


  Abstract

BACKGROUND: The plasminogen activator (PA) and matrix metalloproteinase (MMP) systems are implicated in the establishment of endometriosis. The mechanisms by which these systems are involved in the pathogenesis of this disease are not well defined and controversial results have been published. The aim of this study was to analyse mRNA and protein levels of several components of the PA and MMP systems in endometriotic tissue and endometrium from women with and without endometriosis. METHODS and RESULTS: Real-time quantitative RT-PCR assays were developed to quantify mRNA levels of these components in 57 women with endometriosis and 32 controls. Endometrium of women with endometriosis showed higher mRNA and antigenic levels of urokinase type-PA (uPA) and MMP-3 than endometrium from controls. In these patients, ovarian endometriotic tissue had higher mRNA and antigenic levels of PA inhibitor type 1 (PAI-1) and MMP inhibitor type 1 (TIMP-1) than endometrium. CONCLUSIONS: The increase in mRNA and protein levels of uPA and MMP-3 observed in endometrium of women with endometriosis may facilitate the attachment of endometrial tissue to the peritoneum and ovarian surface, as well as the invasion of the extracellular matrix. This process would lead to the formation of early endometriotic lesions. Once the ovarian endometriotic cyst is developed, PAI-1 and TIMP-1 would increase which could explain the frequent clinical finding of an endometrioma without invasion of the adjacent ovarian tissue.

Keywords: endometriosis; inhibitors; matrix metalloproteinase; plasminogen activators; quantitative RT-PCR.

L.Ramón and J.Gilabert-Estellés have contributed similarly in the present article.


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