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

• Published in: Revista Brasileira de ginecologia e obstetrícia Vol. 40; no. 11; pp. 705 - 712
• Main Authors: Brandão, Verônica Cristina Moraes, Meola, Juliana, Garcia, Sergio Britto, Candido-dos-Reis, Francisco José, Poli-Neto, Omero Benedicto, Nogueira, Antonio Alberto, Rosa-e-Silva, Julio Cesar
• Format: Journal Article
• Language: English
• Published: Rio de Janeiro, Brazil Thieme Revinter Publicações Ltda 01-11-2018; Federação Brasileira das Sociedades de Ginecologia e Obstetrícia
• Subjects: Animals; Cell Differentiation; Cell Proliferation; Choristoma - metabolism; Choristoma - pathology; Disease Models, Animal; endometriosis; Endometriosis - metabolism; Endometriosis - pathology; Endometrium - chemistry; Endometrium - metabolism; Endometrium - pathology; Female; Matrix Metalloproteinase 9 - analysis; Matrix Metalloproteinase 9 - biosynthesis; Membrane Proteins - analysis; Membrane Proteins - biosynthesis; Metallothionein - analysis; Metallothionein - biosynthesis; OBSTETRICS & GYNECOLOGY; Original; Original Article; Rabbits; Tissue Inhibitor of Metalloproteinase-2 - analysis; Tissue Inhibitor of Metalloproteinase-2 - biosynthesis; tissue invasion; cell differentiation; cell proliferation; endometriose; diferenciação celular; proliferação celular; endometriosis; invasão tecidual; tissue invasion
• ISSN: 0100-7203; 1806-9339; 1806-9339
• DOI: 10.1055/s-0038-1675612

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.