title: A GFP endometriosis model reveals important morphological characteristics of the angiogenic process that govern benign and malignant diseases.
abstract: Endometriosis involves the growth of endometriotic tissue outside the uterine cavity, and is frequently associated with different malignancies. A well-reported alteration in the disease microenvironment is the proliferation of new blood vessels around the lesions, as part of a necessary repertory to contribute to the invasiveness and development of infiltrating endometriosis. Therefore, the establishment of a reliable experimental model is essential to elucidate the contribution of angiogenesis and to develop new therapeutic approaches to endometriosis treatment. For this purpose we transplanted endometrial fragments from green fluorescent protein (GFP)-mice (n=20) into the peritoneal cavity of wild-type mice (n=20), and then analyzed the morphological changes and the process of angiogenesis. The lesions were cystic and vascularized, and showed morphological hallmarks such as endometrial glands and stroma. An increase in endometriotic lesion vascular density was revealed by immunostaining and RNAm expression for Vegf and its receptor Flk-1, and the lesions were confirmed as a tissue-donor source by GFP fluorescent cells. The same pattern was observed through staining of activated macrophages and an increase of about 25% in the number of macrophage-positive cells was also demonstrated in endometriotic lesions by flow cytometry, which concords with previous data that correlate endometriosis, angiogenesis and inflammation. According to our understanding, this is the first demonstration that the pattern of the angiogenic process in the GFP endometriosis model is very similar to that of cancer. These observations will be useful for investigation of the process of angiogenesis involved in the attachment and invasion of endometrial cells, as well as an in vivo platform model to study the effects of antiangiogenic drugs.
authors.affiliation: Health and Biological Sciences Center, Pharmacy College, State University of East Zone, and Development and Cell Biology Research Program, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Daniel Escorsim
authors.initials: DE
authors.lastname: Machado
authors.affiliation: Development and Cell Biology Research Program, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Antônio
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Health and Biological Sciences Center, Pharmacy College, State University of East Zone, Rio de Janeiro, Brazil.
authors.forename: João Marcos
authors.initials: JM
authors.lastname: Santos
authors.affiliation: Development and Cell Biology Research Program, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Rômulo Medina
authors.initials: RM
authors.lastname: Mattos
authors.affiliation: Health and Biological Sciences Center, Pharmacy College, State University of East Zone, Rio de Janeiro, Brazil.
authors.forename: Thiago Alves
authors.initials: TA
authors.lastname: dos Santos
authors.affiliation: Health and Biological Sciences Center, Pharmacy College, State University of East Zone, Rio de Janeiro, Brazil.
authors.forename: Sergio Henrique
authors.initials: SH
authors.lastname: Seabra
authors.affiliation: Development and Cell Biology Research Program, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Leonardo da Cunha
authors.initials: Lda C
authors.lastname: Boldrini
authors.affiliation: Health and Biological Sciences Center, Pharmacy College, State University of East Zone, Rio de Janeiro, Brazil.
authors.forename: Jamila Alessandra
authors.initials: JA
authors.lastname: Perini
authors.affiliation: Development and Cell Biology Research Program, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. luiz.nasciutti@histo.ufrj.br.
authors.forename: Luiz Eurico
authors.initials: LE
authors.lastname: Nasciutti
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004715:Endometriosis / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D049452:Green Fluorescent Proteins