Relevance of angiogenesis in autoimmune testis inflammation

GUALDONI G; PEREZ C; LUSTIG, LIVIA; JACOBO PV,; HARO DURAND; GUAZZONE VA; SOBARZO CRISTIAN MARCELO,; MS THEAS

BIOSCIENCE REPORTS

PORTLAND PRESS LTD

Año: 2021 p. 1 - 14

0144-8463

AbstractExperimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. The model reflects the testicular pathological changes reported in immunological infertility in men. Progression of EAO in rodents is associated with a significant increase of testicular endothelial cells percentage and interstitial testicular blood vessels pointing out ongoing angiogenic process. Vascular endothelial growth factor A (VEGFA), the main regulator of physiological and pathological angiogenesis is able to stimulate endothelial cell proliferation, chemotaxis, and vascular permeability. The aim of this study was to explore the role of VEGFA in the pathogenesis of testicular inflammation. Our results revealed VEGFA expression in Leydig cells, endothelial cells and macrophages in testis of rats with autoimmune orchitis . The VEGFA content was significantly higher in testicular fluid and serum of rats after the end of immunization period, preceding testicular damage. VEGFR1 is expressed in testicular endothelial cells mainly, while VEGFR2 was detected in germ cells and vascular smooth muscle cells. Both receptors were expressed in testicular interstitial cells. VEGFR2 increased after immunization period in testicular interstitium and VEGFR1 was downregulated in EAO testis. In vivo specific inhibition of VEGFA using bevacizumab reduced incidence and severity of EAO concomitant with a decreased number of testicular blood vessels. Our results unveil the relevance of VEGFA-VEGFR axis during the development of orchitis suggesting that VEGFA might be an early marker of testicular inflammation and bevacizumab a therapeutic tool for treatment of testicular inflammation associated to subfertility or infertility.