Effect of urolithins on endometriosis and angiogenesis in vivo.

SIMONE J; MC CORMACK B; HARO DURAND L; BARAÑAO RI; MERESMAN G; RICCI A; BILOTAS M

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología, SAFIS.; 2023

Introduction: Endometriosis is a chronic disease defined by the growth of endometrial tissue outside the uterine cavity. Current therapeutic options are limited, often failing to alleviate symptoms and having several side effects. Urolithins are natural compounds generated by the human intestinal microbiota from ellagitannins and ellagic acid. In previous studies, we demonstrated that Urolithin A (UA) and B (UB) have anti-proliferative, anti-migratory, anti-invasive, and pro-apoptotic effects, and downregulate the expression of angiogenesis-promoting genes in endometriosis in-vitro.Objectives: Since angiogenesis is one of the major processes involved in endometriotic lesion establishment and progression, the aim of the present work was to evaluate the effect of UA and UB on angiogenesis in endometriosis in-vivo.Methods: Endometriosis was surgically induced in female BALB/c mice. Fifteen days post-surgery mice were treated with a daily i.p. injection of UA, UB, or PBS (Control, C). After 28 days, animals were sacrificed, peritoneal fluid (PF) was collected, and endometriotic-like lesions were counted, measured, removed, and fixed. Vascularized area was assessed by CD31 immunohistochemistry. The in-vivo angiogenic potential of PF from UA, UB, and C mice, or UA and UB alone, was evaluated using the quail chorioallantoic membrane (CAM) bioassay.Results: UA completely prevented the development of endometriotic-like lesions (p