Abstract
For an adequate functionality of corpus luteum (CL), luteal vasculature should be developed. Angiogenesis is controlled by mitogenic and angiostatic factors. Vascular endothelial growth factor (VEGF) is the main factor involved on equine CL angiogenesis. However, other factors like cytokines may participate on its regulation. The aim of the present work was to evaluate the role of: (i) tumor necrosis factor alpha (TNF), interferon gamma (IFN) and Fas Ligand (FasL) on mRNA expression of VEGF, VEGFR2, thrombospondin 1 (TSP1) and its receptor CD36 in equine luteal cells, throughout the luteal phase; and (ii) on VEGF protein expression in cells from mid luteal phase CL (mid CL). Besides, the effect of VEGF on mid CL secretory capacity (progesterone - P4 and prostaglandin E2 - PGE2) was addressed. In the early CL, TNF increased mRNA expression of VEGF and VEGFR2 and reduced CD36, which was also decreased by IFN, FasL and TNF+IFN+FasL. In mid CL, TNF increased mRNA expression and protein of VEGF and reduced mRNA expression of CD36, FasL and TNF+IFN+FasL decreased VEGF protein expression. In the late CL, TNF and TNF+IFN+FasL reduced mRNA expression of VEGFR2 and TNF+IFN+FasL increased TSP1 and CD36. In mid CL VEGF (50 ng/ml) stimulated P4 and PGE2 secretion. The regulatory role of cytokines on angiogenic/antiangiogenic factors expression and the role of VEGF on luteal secretory capacity were shown, for the first time in the equine CL. The present study substantiates the importance of the immune system on vascular dynamics regulation and secretory function.
