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Hum. Reprod. Advance Access originally published online on March 3, 2005
Human Reproduction 2005 20(6):1695-1701; doi:10.1093/humrep/deh794
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Interleukin 1{alpha} and tissue-lytic matrix metalloproteinase-1 are elevated in ectopic endometrium of patients with endometriosis

G. Hudelist1,2,7, H. Lass3, J. Keckstein2, I. Walter4, F. Wieser5, R. Wenzl5, R. Mueller6, K. Czerwenka6, E. Kubista1 and C.F. Singer1

1 Department of Obstetrics and Gynecology, Division of Special Gynecology, Vienna Medical University, 1090 Vienna, 2 Department of Obstetrics and Gynaecology, LKH Villach, 9500 Villach, 3 Department of Obstetrics and Gynecology, Wilhelminenspital, 1060 Vienna, 4 Department of Histology/Embryology, University of Veterinary Medicine, 1200 Vienna, 5 Department of Obstetrics and Gynecology, Division of Endocrinology and Reproductive Medicine, 6 Department of Clinical Pathology, Division of Gynaecopathology, Vienna Medical University, 1090 Vienna, Austria

7 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, LKH Villach, Nikolaigasse 43, A–9500 Villach, Austria. Email: gernot_hudelist{at}yahoo.de

BACKGROUND: Matrix metalloproteinases (MMP) play an essential role in tissue remodelling and menstruation and appear to be regulated by cytokines such as interleukin-1{alpha} (IL-1{alpha}). In order to investigate their role in the pathogenesis of endometriosis, the aim of the present study was to compare the protein localization of matrix metalloproteinase-1 (MMP-1) and of its main stimulatory cytokine IL-1{alpha} in eutopic and dystopic endometrium of patients with endometriosis. METHODS: MMP-1 and IL-1{alpha} protein localization was analysed retrospectively in paired paraffin-embedded tissue biopsies obtained simultaneously from the endometrial cavity and from endometrial lesions of 37 patients with peritoneal or ovarian endometriosis and in cycling endometria from 37 women without endmetriosis. Protein localization was demonstrated by immunohistochemistry; antibody specifity was confirmed by western blot analysis. RESULTS: MMP-1 and IL-1{alpha} protein staining in women suffering from endometriosis was significantly more pronounced in endometriotic lesions than in eutopic endometrium. This held true for both epithelial MMP-1 and IL-1{alpha} staining (P<0.006 and P<0.001), and for stromal MMP-1 and IL-1{alpha} staining (P<0.001 and P<0.001). Furthermore, stromal MMP-1 and IL-1{alpha} were significantly co-expressed in dystopic endometriotic tissue (P=0.045). Endometrial MMP-1 and IL-1{alpha} protein expression pattern in eutopic endometrium from women suffering from endometriosis, however, did not differ significantly from the pattern seen in healthy women. CONCLUSIONS: The increased expression of both matrix-degrading MMP-1 and its major stimulatory cytokine IL-1{alpha} in endometriotic lesions and the selective co-expression in the stroma of endometriotic foci clearly suggests their involvement in the pathogenic mechanisms leading to local invasion and tissue destruction.

Key words: endometriosis/IL-1{alpha}/MMP-1


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