Relevance of angiogenesis in autoimmune testis inflammation

GUALDONI GISELA; JACOBO, PATRICIA VERÓNICA; SOBARZO CRISTIAN MARCELO,; LUSTIG, LIVIA; THEAS, MARÍA SUSANA; GUAZZONE VANESA ANABELLA

CHICAGO

Congreso; Annual Meeting of the American Society for Reproductive Immunology; 2017

American Society for Reproductive Immunology

Problem: Experimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. The rodent model reflects very well 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) toghether with the increased number of interstitial testicular blood vessels. Vascular endothelial growth factor A (VEGFA) is the main regulator of physiological and pathological angiogenesis by stimulation of endothelial cell proliferation and chemotaxis and increase 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 Wistar adult rats by active immunization with testis homogenate and adjuvants. Bevacizumab (Avastin, Roche) or vehicle was administrated i.p. to rats after the immunization period. VEGFA and VEGF receptors were studied by immunohistochemistry and Western blot or ELISA.Results: VEGFA is expressed in Leydig, EC and testicular macrophages in EAO testis. VEGFA content was higher in testicular fluid and serum after the end of immunization period, preceding testicular lesion. However it is downregulate in both samples when histopathological orchitis is observed. VEGFR1 is expressed mainly in testicular EC, while VEGFR2 was found in germ cell and vascular smooth muscle cells. Furthermore, both receptors are expressed in testicular interstitial cells. VEGFR2 increases after immunization period in testicular interstitium and both receptors are downregulated in EAO testis. Additionally, in vivo specific inhibition of VEGFA using bevacizumab reduced incidence and severity of EAO documented by 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 treatment associate with inflammatory process.