Physiopathology of Peyronie s Disease

• Grant number: 18/14127-6
• Support type: Regular Research Grants
• Duration: August 01, 2019 - July 31, 2020
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal researcher: Sidney Glina
• Grantee: Sidney Glina
• Home Institution: Centro Universitário Saúde ABC. Fundação do ABC. Santo André , SP, Brazil
• Assoc. researchers: Maria Aparecida da Silva Pinhal

Abstract

Peyronie's Disease (PD) affects up to 9% of men older than 50 years and has a highly adverse impact on the quality of life of patients and partners, because of the impairment of sexual performance and accompanying low self-esteem. PD's pathophysiology is not completely understood (1). Apparently, there is a disturbance of the healing mechanism of the tunica albuginea, which can be damaged by micro-traumas and blood extravasation to the tunica albuginea during sexual intercourse. This disorder leads to the formation of a fibrous plaque, which results in a non-distensible area of tunica albuginea, which causes penile deformity during erection. Accumulating evidence suggests that the overexpression of transforming growth factor-² (TGF-²1) may be associated with the pathogenesis of PD (2). This protocol is part of a research line which aims to reproduce the mechanism of the plaque formation on the albuginea on DP (3). In previous study we reproduced some of those alteration by injecting rat blood in the tunica albuginea of the animal, however we were not able to produce the fibrous plaque (4). The aim of this study is to evaluate if the injection of plasma, richer in TGF-beta, isolated or repeated four times, amplify extracellular matrix alterations leading to the plaque formation and to the penile deformities. Methods. The experiment will have two phases: Phase 1: There will be used 15 male rats of specie Rattus novergicus, lineage Wistar divided in 3 groups: control group 15 days ( 5 rats) which will receive an instillation of 20ul distilled water on TA plus penectomy after 15 days; Experimental group 15 days (5 rats) which will receive an instillation of 20ul of plasma obtained of the animal on TA plus penectomy after 15 days; Experimental group 45 days (5 rats) which will receive an instillation of 20ul of plasma obtained of the animal on TA plus penectomy after 45 days. Phase 2 There will be used 15 male rats of specie Rattus novergicus, lineage Wistar divided in 3 groups (10 rats each); Group 1 - instillation of 20ul of plasma obtained of the animal on TA; Grupo 2 - instillation of 20ul distilled water on TA e Grupo 3 - puncture with the same needle used to do the others instillations without any injection to create the trauma. It will be done one procedure per week during 4 consecutive weeks. The animals will be submitted to penectomy 45 days after the last procedure. Before the penectomy it will be done an injection of saline into the corpora cavernosa to mimic an erection to identify possible penile deformities (curvature). There will be done histologic analyses with hematoxylin-eosin (to evaluate the inflammatory process and micro vessels); Trichome of Masson (fibrosis) e Picrosirius ( Collagen type I and III). The samples will be submitted to immunohistochemistry (IHQ) and the expression of proteoglycans and collagen will be evaluated by fluorescence confocal microscopy.References:1. Toscano L Jr, Rezende MV, Mello LF, Paulillo D, Glina S. A prospective, randomized, single - blind study comparing intraplaque injection of thiocolchicine and verapamil in Peyronie's Disease: a pilot study. Int Braz J Urol. 2016 Sep-Oct;42(5):1005-1009.2. Chung E, Ralph D, Kagioglu A, Garaffa G, Shamsodini A, Bivalacqua T, Glina S,Hakim L, Sadeghi-Nejad H, Broderick G. Evidence-Based Management Guidelines onPeyronie's Disease. J Sex Med. 2016 Jun;13(6):905-233. Watanabe MS, Theodoro TR, Coelho NL, Mendes A, Leonel MLP, Mader AM, Nader HB, Glina S, Pinhal MAS. Extracellular matrix alterations in the Peyronie's disease. J Adv Res. 2017 Jul;8(4):455-461.4. Cohen DJ, Oliveira AV, Theodoro TR, Petri G, Melo CM, Cavalheiro RP, Nader HB, Mader AM, Pinhal MAS, Glina S. Extracellular matrix alterations after blood instillation in tunica albuginea of rats. Int J Impot Res. 2017 Dec 15. doi:10.1038/s41443-017-0015-1. (AU)