INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Relevance of angiogenesis in autoimmune testis inflammation
Autor/es:
GUALDONI GISELA; JACOBO PATRICIA V.; SOBARZO CRISTIAN ; THEAS MARÍA S.; LUSTIG LIVIA; GUAZZONE VANESA A.
Lugar:
Chicago
Reunión:
Congreso; American Society of Reproductive Immunology. Annual Meeting 2017; 2017
Resumen:
Problem: Experimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. The rodent model mimics the pathological changes reported in immunological infertility in men. EAO is characterized by interstitial inflammatory cell infiltrates, apoptosis, and sloughing of germ cells leading to aspermatogenesis and infertility. Progression of EAO in rodents is associated with a significant increase of testicular endothelial cells (EC) percentage and increased number of interstitial testicular blood vessels pointing out ongoing angiogenetic process. Vascular endothelial growth factor A (VEGFA), the principal regulator of angiogenesis stimulates endothelial cell proliferation, chemotaxis, and increases vascular permeability. The aim of this study is to explore the role of VEGFA in the pathogenesis of testicular inflammation.Method of Study: EAO was induced in adult Wistar rats by active immunization with testis homogenate and adjuvants. The expression/content of VEGFA and VEGF receptors were studied by immunohistochemistry, Western blot or ELISA.Bevacizumab (Avastin, Roche) or vehicle was administrated i.p. to rats after the immunization period. Results: VEGFA is expressed in Leydig, EC and testicular macrophages in EAO testis. The VEGFA content was significantly higher in testicular fluid and serum of rats after the end of immunization period, preceding testicular damage. In contrast, VEGFA was downregulated when orchitis developed.VEGFR1 is expressed in testicular EC 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 both receptors were 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. Conclusions: Our results unveil the relevance of VEGFA-VEGFR axis during the development of orchitis suggesting a possible therapeutic use of bevacizumab in infertility associated with testicular inflammation.