Characterization and differential expression of vascular endothelial growth factor isoforms and receptors in swine corpus luteum throughout estrous cycle

Abstract

Corpus luteum (CL) undergoes growth and regression during each estrous cycle; these processes are accompanied by growth and regression of the luteal vascular bed. Vascular endothelial growth factor (VEGF) is the main regulator of angiogenesis, inducing endothelial cell proliferation, migration, vascular permeability, and vessel lumen formation. VEGF presents several isoforms that are produced by alternative splicing of the same mRNA transcript. We determined by real time RT-PCR the expression patterns of VEGF isoform and receptor mRNAs, as well as the VEGF protein levels in pig CL throughout a whole estrous cycle. Four novel VEGF isoforms (VEGF144, VEGF147, VEGF182, and VEGF164b) were found for the first time in swine and the seven identified isoforms can be grouped in four different patterns of expression. The most expressed splice variants were VEGF120 and VEGF164. All isoforms showed their highest mRNA levels in newly formed CLs (day 1), followed by a decrease during mid-late luteal phase (days 10-17), except for VEGF182, VEGF188 and VEGF144 that showed a differential regulation during late luteal phase (day 14) or at luteolysis (day 17). VEGF protein levels paralleled the most expressed and secreted VEGF120 and VEGF164 isoforms. The VEGF receptors mRNAs showed a different pattern of expression in relation to their ligands, increasing between day 1 and 3 and gradually decreasing during the mid-late luteal phase. The differential regulation of VEGF isoforms may suggest specific physiological roles for some of them, particularly in angioregression occurring during the apoptotic structural luteolysis.