A GFP endometriosis model reveals important morphological characteristics of the angiogenic process that govern benign and malignant diseases.

A GFP endometriosis model reveals important morphological characteristics of the angiogenic process that govern benign and malignant diseases Daniel Escorsim Machado1,2, Antônio Palumbo Júnior2, João Marcos Santos1, Rômulo Medina Mattos2, Thiago Alves dos Santos1, Sergio Henrique Seabra1, Leonardo da Cunha Boldrini2, Jamila Alessandra Perini1 and Luiz Eurico Nasciutti2 1Health and Biological Sciences Center, Pharmacy College, State University of East Zone, Rio de Janeiro, Brazil and 2Development and Cell Biology Research Program, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Offprint requests to: Luiz Eurico Nasciutti, Laboratório de Interaçoes Celulares, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária - Ilha do Fundao, 21941-590, Rio de Janeiro, Brazil. e-mail: [email protected] Summary. 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. Histol Histopathol 29, 903-912 (2014) Key words: Endometriosis, GFP mice, Angiogenesis, VEGF DOI: 10.14670/HH-29.903