Increased Expression Levels of Metalloprotease, Tissue Inhibitor of Metalloprotease, Metallothionein, and p63 in Ectopic Endometrium: An Animal Experimental Study

Verônica Cristina Moraes Brandão, Juliana Meola, Sérgio Britto Garcia, Sergio Britto Garcia, Francisco José Candido-Dos-Reis, Francisco José Cândido dos Reis, Omero Benedicto Poli-Neto, Omero Benedicto Poli‐Neto, Antonio Alberto Nogueira, Antônio Alberto Nogueira, Júlio César Rosa e Silva, Julio Cesar Rosa-E-Silva
Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2018 · vol. 40(11) , pp. 705–712 · doi:10.1055/s-0038-1675612 · PMID:30485900 · PMC10316939 · W2902336160
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Ectopic endometria in rabbits exhibited increased expression of MMP-9, TIMP-2, MT, and p63 compared to eutopic endometria, indicating greater potential for cell differentiation and tissue invasion.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-08 ⓘ

This animal experimental study induced endometriosis-like lesions in 29 female New Zealand rabbits and compared eutopic versus ectopic endometrial tissues at 4 and 8 weeks after endometrial implantation. Using immunohistochemistry on excised lesions, the authors found higher staining intensity for metalloprotease (MMP-9), tissue inhibitor of metalloprotease (TIMP-2), metallothionein (MT), and p63 in ectopic endometrium than in eutopic endometrium, indicating greater invasive and differentiation/proliferation marker expression. When ectopic lesions were compared between 4 and 8 weeks, there was no significant difference for MMP-9, TIMP-2, and MT, except p63, which was more evident at 8 weeks. The study’s main limitation is its use of a rabbit model without hormonal supplementation and evaluation limited to marker expression at these two time points. This paper is centrally about endometriosis — an animal study characterizing invasive and differentiation/proliferation-related marker expression differences between eutopic and ectopic endometrial tissue.

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Abstract

OBJECTIVE: To characterize the patterns of cell differentiation, proliferation, and tissue invasion in eutopic and ectopic endometrium of rabbits with induced endometriotic lesions via a well- known experimental model, 4 and 8 weeks after the endometrial implantation procedure. METHODS: Twenty-nine female New Zealand rabbits underwent laparotomy for endometriosis induction through the resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of animals (one with 14 animals, and the other with15) were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised along with the opposite uterine horn for endometrial gland and stroma determination. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissues for analysis of the following markers: metalloprotease (MMP-9) and tissue inhibitor of metalloprotease (TIMP-2), which are involved in the invasive capacity of the endometrial tissue; and metallothionein (MT) and p63, which are involved in cell differentiation and proliferation. RESULTS: The intensity of the immunostaining for MMP9, TIMP-2, MT, and p63 was higher in ectopic endometria than in eutopic endometria. However, when the ectopic lesions were compared at 4 and 8 weeks, no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue. CONCLUSION: Ectopic endometrial lesions seem to express greater power for cell differentiation and tissue invasion, compared with eutopic endometria, demonstrating a potentially invasive, progressive, and heterogeneous presentation of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Choristoma Endometriosis Endometrium Matrix Metalloproteinase 9 Membrane Proteins Metallothionein Tissue Inhibitor of Metalloproteinase-2 Animals Cell Differentiation Cell Proliferation Choristoma Choristoma Disease Models, Animal Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Matrix Metalloproteinase 9

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