MMP-9 and TIMP-1 Promote Extracellular Matrix Remodeling in the Formation of Ovarian Endometrioma: in vitro Study on Chicken Chorioallantoic Membrane

Vidia Sari, Riris Istighfari Jenie, Shofwal Widad, Agung Dewanto
In: The Indonesian Biomedical Journal · 2023 · vol. 15(1) , pp. 69–76 · doi:10.18585/inabj.v15i1.2090 · W4321482955
article OA: gold CC0
🔓 Open OA copy Full text JSON View on OpenAlex View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-09 ⓘ

This study found that increased MMP-9 activity and decreased TIMP-1 expression correlate with endometrioma tissue invasion in the chicken chorioallantoic membrane model.

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, 2026-06-09 · read from full text ⓘ

The paper investigated how matrix metalloproteinase (MMP)-9 activity and tissue inhibitor of metalloproteinase (TIMP)-1 expression relate to extracellular matrix remodeling during early endometrioma development, using endometrioma tissue from 24 women (30 samples) implanted onto a chicken chorioallantoic membrane for five days. Invasion ability was quantified by hematoxylin-eosin staining, while MMP-9 activity was measured by gelatin zymography and TIMP-1 expression by western blot; invasion scores were correlated with these measures using Spearman tests. They found a strong positive correlation between MMP-9 activity and invasion scores (r=0.656, p=0.000) and a weak negative correlation with TIMP-1 expression (r=-0.388, p=0.034). The study is limited by its in vitro CAM model and by using correlations rather than experimentally manipulating MMP-9 or TIMP-1. This paper is centrally about endometriosis — specifically early ovarian endometrioma invasion linked to MMP-9 activity and TIMP-1 expression during extracellular matrix remodeling.

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

Abstract

BACKGROUND: The invasion of endometrial tissue in the peritoneal layers is an important precursor to the formation of endometriosis. However, the mechanisms of the initial development of endometrioma remain unclear. This study aimed to explore the correlation between matrix metalloproteinase (MMP)-9 activity and tissue inhibitors of metalloproteinase (TIMP)-1 expression in the initial development of endometriosis through the invasion process of endometrial lesions in extracellular matrix (ECM) remodeling.METHODS: A total of 30 samples of endometrioma tissue were obtained from 24 women with endometriosis and examined at Dr. Sardjito General Hospital, Yogyakarta, Indonesia. The tissue was then implanted into a chicken chorioallantoic membrane (CAM) for five days to examine its invasion ability. The invasion scores were assessed using hematoxylin-eosin staining. MMP-9 activity and TIMP-1 expression were analyzed using gelatin zymography and western blot, respectively. The correlations between MMP-9 activity and TIMP-1 expressions with the invasion scores were analyzed using Spearman correlation tests with significance set as p<0.05.RESULTS: The results showed that there was a strong positive correlation between MMP-9 activity and invasion scores of endometriomas tissue (r=0.656; p=0.000). Meanwhile, expression levels of TIMP-1 had a weak negative correlation with the increase of invasion scores of endometrioma (r=-0.388; p=0.034). These results indicate the involvement of MMP-9 and TIMP-1 in the initial development of endometriosis during the ECM remodeling.CONCLUSION: MMP-9 activity and TIMP-1 expression were correlated with the invasion score of endometrioma tissue. This study provides evidence for understanding the mechanisms involved in ECM remodeling in the early process of endometriosis.KEYWORDS: endometrioma, extracellular matrix remodeling, MMP-9, TIMP-1
Full text 8,663 characters · extracted from oa-doi-fallback · 6 sections · click to expand

Abstract

BACKGROUND: The invasion of endometrial tissue in the peritoneal layers is an important precursor to the formation of endometriosis. However, the mechanisms of the initial development of endometrioma remain unclear. This study aimed to explore the correlation between matrix metalloproteinase (MMP)-9 activity and tissue inhibitors of metalloproteinase (TIMP)-1 expression in the initial development of endometriosis through the invasion process of endometrial lesions in extracellular matrix (ECM) remodeling.

Methods

A total of 30 samples of endometrioma tissue were obtained from 24 women with endometriosis and examined at Dr. Sardjito General Hospital, Yogyakarta, Indonesia. The tissue was then implanted into a chicken chorioallantoic membrane (CAM) for five days to examine its invasion ability. The invasion scores were assessed using hematoxylin-eosin staining. MMP-9 activity and TIMP-1 expression were analyzed using gelatin zymography and western blot, respectively. The correlations between MMP-9 activity and TIMP-1 expressions with the invasion scores were analyzed using Spearman correlation tests with significance set as p<0.05.

Results

The results showed that there was a strong positive correlation between MMP-9 activity and invasion scores of endometriomas tissue (r=0.656; p=0.000). Meanwhile, expression levels of TIMP-1 had a weak negative correlation with the increase of invasion scores of endometrioma (r=-0.388; p=0.034). These results indicate the involvement of MMP-9 and TIMP-1 in the initial development of endometriosis during the ECM remodeling.

Conclusion

MMP-9 activity and TIMP-1 expression were correlated with the invasion score of endometrioma tissue. This study provides evidence for understanding the mechanisms involved in ECM remodeling in the early process of endometriosis.

Keywords

endometrioma, extracellular matrix remodeling, MMP-9, TIMP-1

References

Bałkowiec M, Maksym RB, Włodarski PK. The bimodal role of matrix metalloproteinases and their inhibitors in etiology and pathogenesis of endometriosis. Mol Med Rep. 2018; 18(3): 3123-36, CrossRef. Kapoor R, Stratopoulou CA, Dolmans MM. Pathogenesis of endometriosis: New insights into prospective therapies. Int J Mol Sci. 2021; 22(21): 11700, CrossRef. Carnahan M, Fedor J, Agarwal A, Gupta S. Ovarian endometrioma: Guidelines for selection of cases for surgical treatment or expectant management. Expert Rev Obstet Gynecol. 2013; 8: 29–55, CrossRef. Saragih CF, Rivany R, Sahil MF, Fadjrir F, Ardiansyah E, Yaznil MR, et al. The difference of Bax protein expression between endometrioma and ovarian carcinoma. Mol Cell Biomed Sci. 2019; 3(2): 95–9, CrossRef. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Eng J Med. 2020; 382(13): 1244–56, CrossRef. Young VJ, Brown JK, Saunders PTK, Horne AW. The role of the peritoneum in the pathogenesis of endometriosis. Hum Reprod Update. 2013; 19(5): 558–69, CrossRef. Hogg C, Horne AW, Greaves E. Endometriosis-associated macrophages: Origin, phenotype, and function. Front Endocrinol. 2020; 11: 7, CrossRef. Ke J, Ye J, Li M, Zhu Z. The role of matrix metalloproteinases in endometriosis: A potential target. Biomolecules. 2021; 11(11): 1739, CrossRef. Osteen KG, Yeaman GR, Bruner-Tran KL. Matrix metalloproteinases and endometriosis. Semin Reprod Med. 2003; 21(2): 155–64, CrossRef. Henriet P, Mon KS, Marbaix E. Are matrix metalloproteinases and their inhibitors reliable diagnosis biomarkers and attractive therapeutic targets in endometriosis? Met Med. 2016; 3: 81–92, CrossRef. Pitsos M, Kanakas N. The role of matrix metalloproteinases in the pathogenesis of endometriosis. Reprod Sci. 2009; 16(8): 717–26, CrossRef. Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): An ancient family with structural and functional diversity. Biochim Biophys Acta Mol Cell Res. 2010; 1083(1): 55–71, CrossRef. Barbe AM, Berbets AM, Davydenko IS, Koval HD, Yuzko VO, Yuzko OM. Expression and significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in endometriosis. J Med Life. 2020; 13(3): 314–20, CrossRef. Suryawan A, Mose JC, Handono B. MMP-9 level comparation between spontaneous abortion and normal pregnancy. Indones Biomed J. 2012; 4(3): 174–9, CrossRef. Collette T, Bellehumeur C, Kats R, Maheux R, Mailloux J, Villeneuve M, et al. Evidence for an increased release of proteolytic activity by the eutopic endometrial tissue in women with endometriosis and for involvement of matrix metalloproteinase-9. Hum Reprod. 2004; 19(6): 1257–64, CrossRef. Gershtein ES, Mushtenko SV, Ermilova VD, Levchenko NE, Kushlinskii NE. Matrix metalloproteinases and their tissue inhibitors in blood serum of patients with endometrial cancer: Clinical and morphological correlations. Bull Exp Biol Med. 2018; 165(1): 75–9, CrossRef. Dayer C, Stamenkovic I. Recruitment of matrix metalloproteinase-9 (MMP-9) to the fibroblast cell surface by lysyl hydroxylase 3 (LH3) triggers transforming growth factor-β (TGF-β) activation and fibroblast differentiation. J Biol Chem. 2015; 290(22): 13763–78, CrossRef. Madjid TH, Ardiansyah DF, Permadi W, Hernowo B. Expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in endometriosis menstrual blood. Diagnostics. 2020; 10(6): 364, CrossRef. Witz CA, Montoya-Rodriguez IA, Cho S, Centonze VE, BonewaldLF, Schenken RS. Composition of the extracellular matrix of the peritoneum. J Soc Gynecol Investig. 2001; 8(5): 299–304, CrossRef. Maas JWM, Groothuis PG, Dunselman GAJ, de Goeij AFPM, Struijker-Boudier HAJ, Evers JLH. Development of endometriosis-like lesions after transplantation of human endometrial fragments onto the chick embryo chorioallantoic membrane. Hum Reprod. 2001; 16(4): 627–31, CrossRef. Nap AW, Dunselman GAJ, de Goeij AFPM, Evers JLH, Groothuis PG. Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model. Hum Reprod. 2004; 19(10): 2180–7, CrossRef. Dewanto A, Khasanah N. Protokol Penelitian: Panen Jaringan Implan pada Chick Chorioallantoic Membrane. Yogyakarta: Fakultas Kedokteran, Universitas Gadjah Mada; 2016. Pluchino N, Poppi G, Yart L, Marci R, Wenger JM, Tille JC, et al. Effect of local aromatase inhibition in endometriosis using a new chick embryo chorioallantoic membrane model. J Cell Mol Med. 2019; 23(8): 5808–12, CrossRef. Jana S, Chatterjee K, Ray AK, Dasmahapatra P, Swarnakar S. Regulation of matrix metalloproteinase-2 activity by COX-2-PGE2-pAKT axis promotes angiogenesis in endometriosis. PLoS One. 2016; 11(10): e0163540, CrossRef. Nap AW, Groothuis PG, Demir AY, Maas JWM, Dunselman GAJ, de Goeij AFPM, et al. Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane. Hum Reprod. 2003; 18(1): 30–4, CrossRef. Toth M, Fridman R. Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography. Methods Mol Med. 2001; 57: 163–74, CrossRef. Jenie RI, Handayani S, Susidarti RA, Udin LZ, Meiyanto E. The cytotoxic and antimigratory activity of brazilin-doxorubicin on MCF-7/HER2 cells. Adv Pharm Bull. 2018; 8(3): 507–16, CrossRef. Stamenkovic I. Extracellular matrix remodelling: The role of matrix metalloproteinases. J Pathol. 2003; 200(4): 448–64, CrossRef. Szamatowicz J, Laudan ́ski P, Laudan ́ski L, Tomaszewska I. Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1: A possible role in the pathogenesis of endometriosis. Hum Reprod. 2002; 17(2): 284–8, CrossRef. Zafrakas M, Kotronis K, Papasozomenou P, Eskitzis P, Grimbizis G. Extracellular matrix metalloproteinases in the etiopathogenesis of endometriosis: A systematic review and critical appraisal. Clin Exp Obstet Gynecol. 2020; 47(2): 147–53, CrossRef. Pan H, Sheng JZ, Tang L, Zhu R, Zhou TH, Huang HF. Increased expression of c-fos protein associated with increased matrix metalloproteinase-9 protein expression in the endometrium of endometriotic patients. Fertil Steril. 2008; 90(4): 1000–7, CrossRef. Mizumoto H, Saito T, Ashihara K, Nishimura M, Takehara M, Tanaka R, et al. Expression of matrix metalloproteinases in ovarian endometriomas: Immunohistochemical study and enzyme immunoassay. Life Sci. 2002; 71(3): 259–73, CrossRef. DOI: https://doi.org/10.18585/inabj.v15i1.2090 Copyright (c) 2023 The Prodia Education and Research Institute This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Indexed by: The Prodia Education and Research Institute

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

endometriosisendometrioma

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 (30)

Source provenance

openalex
last seen: 2026-06-04T00:00:01.174412+00:00
License: CC0 · commercial use OK