Hum. Reprod. Advance Access originally published online on July 31, 2006
Human Reproduction 2006 21(12):3059-3067; doi:10.1093/humrep/del297
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Increased expression of matrix metalloproteinase-9 in the eutopic endometrial tissue of women with endometriosis
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, Canada G1L 3L5. E-mail: ali.akoum{at}crsfa.ulaval.ca
BACKGROUND: Endometriosis is a disease where endometrial tissue implants in ectopic locations. Remodelling of the extracellular matrix (ECM) is a prerequisite for the implantation of this tissue to be possible. METHODS: In this study, we detected immunoreactive matrix metalloproteinase-9 (MMP-9) throughout endometrial tissue and identified von Willebrand factor (vWF)-positive endothelial cells, CD45-positive leukocytes, CD3-positive T lymphocytes and CD68-positive macrophages as cells expressing MMP-9 in the stroma. RESULTS: We found an increased expression of MMP-9 in the uterine endometrial tissue of women with endometriosis, as assessed by zymography and enzyme-linked immunosorbent assay (ELISA) (P < 0.05). However, RT–PCR did not show a statistically significant increase in MMP-9 mRNA expression in these tissues (P = 0.14). There was no significant difference between women with and without endometriosis in the expression of tissue inhibitor of MMPs (TIMP)-1, a known natural inhibitor of the pro- and active forms of MMP-9, whether tested by ELISA or by RT–PCR (P = 0.46 and 0.37, respectively). Interestingly, the ratio of MMP-9/TIMP-1 expression was significantly higher in women with endometriosis than in normal women both at the protein and the mRNA levels (P < 0.05). CONCLUSION: These findings make plausible the involvement of MMP-9/TIMP-1 imbalance in the invasiveness of the endometrial tissue of patients with endometriosis and the ectopic development of the disease.
Key words: endometriosis/endometrium/matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase
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