Hum. Reprod. Advance Access originally published online on April 22, 2004
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Human Reproduction, Vol. 19, No. 6, 1257-1264,
June 2004
© 2004 European Society of Human Reproduction and Embryology
Evidence for an increased release of proteolytic activity by the eutopic endometrial tissue in women with endometriosis and for involvement of matrix metalloproteinase-9
1 Centre de Recherche, Hôpital Saint-François d’Assise, Centre Hospitalier Universitaire de Québec and 2 Département d’Obstétrique et Gynécologie, Faculté de Médecine, Université Laval, Québec, Canada
3 To whom correspondence should be addressed at: Unité d’Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d’Assise, Centre Hospitalier Universitaire de Québec, 10 rue de l’Espinay, Local D0-711, Québec, Québec, Canada, G1L 3L5. e-mail: ali.akoum{at}crsfa.ulaval.ca
BACKGROUND: For the implantation of endometrium in ectopic locations, remodelling of the extracellular matrix (ECM) is necessary. Many studies have shown an increased expression of various proteases in the ectopic endometrium of women with endometriosis. Few, however, have addressed possible changes in protease expression in the eutopic endometrium. METHODS AND RESULTS: Herein, we reveal an increased release of proteolytic activity by the eutopic endometrium of women with endometriosis compared with normal women (P < 0.01). Using zymography and western blotting, we identified matrix metalloproteinase (MMP)-2 and MMP-9 in the culture medium, and further found that MMP-9 secretion, as assessed by zymography and enzyme-linked immunosorbent assay (ELISA), was elevated in women with endometriosis compared with normal women (P < 0.05). No statistically significant difference in MMP-2 secretion between women with and without endometriosis was noted. However, a significant difference in the levels of the tissue inhibitor of metalloproteinases (TIMP)-1, a known MMP-9 inhibitor, was found (P < 0.05). CONCLUSION: The endometriosis-associated increase in proteolysis and imbalance between the secretion of MMP-9 and that of its natural inhibitor, TIMP-1, revealed in the culture medium of endometrial tissue may reflect in vivo the enhanced capacity of this tissue to break down the ECM in host tissues, thereby favouring its ectopic implantation and development.
Key words: endometriosis/MMP-9/proteolysis/TIMP-1
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