title: Cystic endometrial hyperplasia-pyometra syndrome in bitches: identification of hemodynamic, inflammatory, and cell proliferation changes.
abstract: Cystic endometrial hyperplasia (CEH)-pyometra syndrome is one of the most common diseases of noncastrated female dogs. However, determination of etiological mechanisms and differential diagnosis of CEH-pyometra syndrome are undefined. The aim of this study is to compare immunohistochemically the expression of cyclooxygenase-2 (COX-2) inflammatory mediator, Ki-67 antigen proliferation marker, vascular endothelial growth factor (VEGF-A) angiogenesis mediator and its FLT-1 and KDR receptors, and correlate with Doppler velocimetry of uterine artery and endometrial vascularization in bitches with CEH-pyometra syndrome. Bitches were allocated into CEH-mucometra Group (n = 13), Pyometra Group (n = 11), and Control Group (n = 8). Pyometra Group presented cytoplasmatic staining intensity for COX-2, VEGF-A, and FLT-1 and KDR receptors in luminal epithelium cells significantly higher compared to CEH-mucometra and Control groups. For the glandular epithelium, Pyometra Group had higher immunostaining score for VEGF-A and its receptors (FLT-1 and KDR). Hemodynamic indexes showed negative correlation with VEGF-A and its receptors as well as with COX-2. On the other hand, uterine vascularization score showed positive correlation in relation to immunostaining of COX-2, VEGF-A, and receptors in the endometrium luminal epithelium. In conclusion, uterus of bitches with CEH-pyometra syndrome show inflammatory process characterized by COX-2 expression, resulting in greater expression of proliferative Ki-67 marker as tissue response against the infectious agent. Furthermore, the increased VEGF-A expression and its receptors in CEH-pyometra reflect the increased blood flow and lower vascular resistance. Therefore, canine pyometra is characterized by an inflammatory, proliferative, and vascular disorder.
authors.affiliation: Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Gisele Almeida Lima
authors.initials: GA
authors.lastname: Veiga
authors.affiliation: Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Ricardo Henrique
authors.initials: RH
authors.lastname: Miziara
authors.affiliation: Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Daniel Souza Ramos
authors.initials: DS
authors.lastname: Angrimani
authors.affiliation: Department of Surgery, Sector of Anatomy, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Paula Carvalho
authors.initials: PC
authors.lastname: Papa
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cogliati
authors.affiliation: Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Camila Infantosi
authors.initials: CI
authors.lastname: Vannucchi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004283:Dog Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004285:Dogs; D004717:Endometrium / Q000098:blood supply; D005260:Female; D006439:Hemodynamics; D019394:Ki-67 Antigen / Q000378:metabolism; D055112:Pyometra / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D055988:Uterine Artery / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Doppler ultrasonography; bitches; inflammation; pyometra; vascularization