Eutopic endometrium and peritoneal, ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases-2, -3 and -11, and of tissue inhibitor metalloproteinases-1 and -2

Uzan C, Catherine Uzan, Cortez A, A. Cortez, Annie Cortez, Dufournet C, Charlotte Dufournet, Raffaèle Fauvet, Raffa�le Fauvet, Fauvet R, Jean-Pierre Siffroi, Jean‐Pierre Siffroi, Siffroi JP, Emile Dara�, Emile Daraï, Daraï E
Virchows Archiv : an international journal of pathology · 2004 · vol. 445(6) , pp. 603–609 · doi:10.1007/s00428-004-1117-y · PMID:15452706 · W2009931310
article OA: closed CC0 ⤵ 51 in-corpus citations
Full text JSON View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06+body, 2026-06-24 ⓘ

Eutopic endometrium, peritoneal, ovarian, and bowel endometriotic tissues show differing expressions of MMPs and TIMPs, with MMP-2, -3, and TIMP-2 potentially playing roles in endometriosis pathogenesis and lesion invasiveness.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This study used immunohistochemistry to compare expression of matrix metalloproteinases (MMP-2, MMP-3, MMP-11) and tissue inhibitors (TIMP-1, TIMP-2) in eutopic endometrium from women with or without endometriosis and in peritoneal, ovarian, and colorectal endometriotic tissues. Women with endometriosis had decreased eutopic endometrial MMP-2 expression and loss of MMP-3 expression compared with controls, while MMP-11, TIMP-1, and TIMP-2 were similar; across lesion sites, MMP-2/-3/-11 were higher in colorectal than in ovarian or peritoneal lesions, and TIMP-2 was lower in colorectal disease and in ovarian endometriotic cysts. TIMP-1 did not vary by lesion location. The paper explicitly frames these findings as suggestive for MMP-2 and MMP-3 and TIMP-2 involvement in endometriosis pathogenesis, but the caveat is its small sample sizes and cross-sectional tissue expression design. This paper is centrally about endometriosis — it maps differential MMP/TIMP profiles across eutopic and peritoneal, ovarian, and bowel lesions.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Endometriosis is subsequent to the ability of endometrial glands to invade normal tissues. Matrix metalloproteinases (MMPs)--enzymes that mediate normal tissue turnover, including endometrial breakdown during menstruation-appear to be involved in this invasive process. Here, we examined the immunohistochemical expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18) in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression compared with women without endometriosis (mean+/-SD positive cells: 24.3+/-28.3% and 69.3+/-12.1%), together with loss of MMP-3 expression (0 versus 17.5%+/-20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups. Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were similar in women with endometriosis and in those with peritoneal endometriosis. MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in peritoneal endometriosis. TIMP-1 expression did not vary according to the location of endometriotic lesions. These results suggest that MMP-2 and -3 and TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2 and -3 overexpression was related to the infiltrative nature of endometriotic lesions, with possible sequential expression from peritoneal to colorectal endometriosis.
Full text 8,672 characters · extracted from oa-doi-fallback · 3 sections · click to expand

Abstract

Endometriosis is subsequent to the ability of endometrial glands to invade normal tissues. Matrix metalloproteinases (MMPs)—enzymes that mediate normal tissue turnover, including endometrial breakdown during menstruation—appear to be involved in this invasive process. Here, we examined the immunohistochemical expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18) in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression compared with women without endometriosis (mean±SD positive cells: 24.3±28.3% and 69.3±12.1%), together with loss of MMP-3 expression (0 versus 17.5%±20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups. Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were similar in women with endometriosis and in those with peritoneal endometriosis. MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in peritoneal endometriosis. TIMP-1 expression did not vary according to the location of endometriotic lesions. These results suggest that MMP-2 and -3 and TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2 and -3 overexpression was related to the infiltrative nature of endometriotic lesions, with possible sequential expression from peritoneal to colorectal endometriosis. Similar content being viewed by others

References

Birkedal-Hansen H, Moore WG, Bodden MK et al (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4:197–250 Bruner-Tran KL, Eisenberg E, Yeaman GR, Anderson TA, McBean J, Osteen KG (2002) Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice. J Clin Endocrinol Metab 87:4782–4791 Bruse C, Bergqvist A, Carlstrom K, Fianu-Jonasson A, Lecander I, Astedt B (1998) Fibrinolytic factors in endometriotic tissue, endometrium, peritoneal fluid, and plasma from women with endometriosis and in endometrium and peritoneal fluid from healthy women. Fertil Steril 70:821–826 Collette T, Bellehumeur C, Kats R, Maheux R, Mailloux J, Villeneuve M, Atloum A (2004) Evidence for an increase release of proteolytic activity by eutopic endometrial tissue in women with endometriosis and for involvement of MMP-9. Human Reprod 19:1257–1264 Cox KE, Piva M, Sharpe-Timms KL (2001) Differential regulation of matrix metalloproteinase-3 gene expression in endometriotic lesions compared with endometrium. Biol Reprod 65:1297–1303 Chung HW, Lee JY, Moon HS et al (2002) Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase, and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium. Fertil Steril 78:787–795 Curry TE Jr, Osteen KG (2001) Cyclic changes in the matrix metalloproteinase system in the ovary and uterus. Biol Reprod 64:1285–1296 Darai E, Leblanc M, Walker-Combrouze F, Bringuier AF, Madelenat P, Scoazec JY (1998) Expression of cadherins and CD44 isoforms in ovarian endometrial cysts. Hum Reprod 13:1346–1352 di Nezza LA, Misajon A, Zhang J et al (2002) Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion. Cancer 94:1466–1475 Fauvet R, Poncelet C, Hugol D, Lavaur A, Feldmann G, Darai E (2003) Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours. Virchows Arch 443:38–43 Gaetje R, Kotzian S, Herrmann G, Baumann R, Starzinski-Powitz A (1995) Invasiveness of endometriotic cells in vitro. Lancet 346:1463–1464 Gagne D, Rivard M, Page M et al (2003) Development of a nonsurgical diagnostic tool for endometriosis based on the detection of endometrial leukocyte subsets and serum CA-125 levels. Fertil Steril 80:876–885 Gilabert-Estelles J, Estelles A, Gilabert J et al (2003) Expression of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis. Hum Reprod 18:1516–1522 Goffin F, Frankenne F, Beliard A et al (2002) Human endometrial epithelial cells modulate the activation of gelatinase a by stromal cells. Gynecol Obstet Invest 53:105–111 Jolicoeur C, Boutouil M, Drouin R, Paradis I, Lemay A, Akoum A (1998) Increased expression of monocyte chemotactic protein-1 in the endometrium of women with endometriosis. Am J Pathol 152:125–133 Kokorine I, Marbaix E, Henriet P et al (1996) Focal cellular origin and regulation of interstitial collagenase (matrix metalloproteinase-1) are related to menstrual breakdown in the human endometrium. J Cell Sci 109:2151–2160 Kokorine I, Nisolle M, Donnez J, Eeckhout Y, Courtoy PJ, Marbaix E (1997) Expression of interstitial collagenase (matrix metalloproteinase-1) is related to the activity of human endometriotic lesions. Fertil Steril 68:246–251 Liokumovich P, Goldberg I, Davidson B, Gotlieb WH, Zahavi T, Ben Baruch G (1999) Expression of metalloproteinases endometrial stromal sarcoma: immunohistochemical study using image analysis. J Clin Pathol 52:198–202 Mizumoto H, Saito T, Ashihara K et al (2002) Expression of matrix metalloproteinases in ovarian endometriomas: immunohistochemical study and enzyme immunoassay. Life Sci 71:259–273 Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–2149 Noble LS, Simpson ER, Johns A, Bulun SE (1996) Aromatase expression in endometriosis. J Clin Endocrinol Metab 81:174–179 Osteen KG, Keller NR, Feltus FA, Melner MH (1999) Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium. Gynecol Obstet Invest 48[Suppl 1]:2–13 Osteen KG, Igarashi TM, Bruner-Tran KL (2003) Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression. Front Biosci 8:78–86 Osteen KG, Yeaman GR, Bruner-Tran KL (2003) Matrix metalloproteinases and endometriosis. Semin Reprod Med 21:155–164 Poncelet C, Leblanc M, Walker-Combrouze F et al (2002) Expression of cadherins and CD44 isoforms in human endometrium and peritoneal endometriosis. Acta Obstet Gynecol Scand 81:195–203 Ria R, Loverro G, Vacca A et al (2002) Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 agree with progression of ovarian endometriomas. Eur J Clin Invest 32:199–206 Ridley JH (1981) Coelomic metaplasia. Am J Obstet Gynecol 140:233–234 Ryan IP, Taylor RN (1997) Endometriosis and infertility: new concepts. Obstet Gynecol Surv 52:365–371 Sampson JA (1927) Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:422–469 Sillem M, Prifti S, Koch A, Neher M, Jauckus J, Runnebaum B (2001) Regulation of matrix metalloproteinases and their inhibitors in uterine endometrial cells of patients with and without endometriosis. Eur J Obstet Gynecol Reprod Biol 95:167–174 Stovall DW, Bowser LM, Archer DF, Guzick DS (1997) Endometriosis-associated pelvic pain: evidence for an association between the stage of disease and a history of chronic pelvic pain. Fertil Steril 68:13–18 Ueda M, Yamashita Y, Takehara M et al (2002) Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis. Gynecol Endocrinol 16:391–402 Vercellini P, Trespidi L, De Giorgi O, Cortesi I, Parazzini F, Crosignani PG (1996) Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril 65:299–304 Wenzl RJ, Heinzl H (1998) Localization of matrix metalloproteinase-2 in uterine endometrium and ectopic implants. Gynecol Obstet Invest 45:253–257 Wingfield M, Macpherson A, Healy DL, Rogers PA (1995) Cell proliferation is increased in the endometrium of women with endometriosis. Fertil Steril 64:340–346

Acknowledgement

We want to thank the “Ligue contre le cancer” for the grant. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Uzan, C., Cortez, A., Dufournet, C. et al. Eutopic endometrium and peritoneal, ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases-2, -3 and -11, and of tissue inhibitor metalloproteinases-1 and -2. Virchows Arch 445, 603–609 (2004). https://doi.org/10.1007/s00428-004-1117-y Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00428-004-1117-y

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Intestinal Diseases Matrix Metalloproteinase 2 Matrix Metalloproteinase 3 Metalloendopeptidases Ovarian Diseases Peritoneal Diseases Tissue Inhibitor of Metalloproteinase-1 Tissue Inhibitor of Metalloproteinase-2 Endometriosis Endometrium Female Humans Immunohistochemistry Intestinal Diseases Matrix Metalloproteinase 11 Matrix Metalloproteinase 2 Matrix Metalloproteinase 3 Metalloendopeptidases

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (36)

Cited by (50)

Source provenance

europepmc
last seen: 2026-08-07T06:07:27.085738+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:12:26.305326+00:00
License: CC0 · commercial use OK