title: Vascular endothelial growth factors C and D may promote angiogenesis in the primate ovulatory follicle.
abstract: Angiogenesis in the ovary occurs rapidly as the ovarian follicle transforms into a mature corpus luteum. Granulosa cells produce vascular endothelial growth factor A (VEGFA) in response to the ovulatory gonadotropin surge. VEGFA is established as a key mediator of angiogenesis in the primate ovulatory follicle. To determine if additional VEGF family members may be involved in angiogenesis within the ovulatory follicle, cynomolgus monkeys (Macaca fascicularis) received gonadotropins to stimulate multiple follicular development, and human chorionic gonadotropin (hCG) substituted for the luteinizing hormone surge to initiate ovulatory events. Granulosa cells of monkey ovulatory follicles contained mRNA and protein for VEGFC and VEGFD before and after hCG administration. VEGFC and VEGFD were detected in monkey follicular fluid and granulosa cell-conditioned culture media, suggesting that granulosa cells of ovulatory follicles secrete both VEGFC and VEGFD. To determine if these VEGF family members can stimulate angiogenic events, monkey ovarian microvascular endothelial cells (mOMECs) were obtained from monkey ovulatory follicles and treated in vitro with VEGFC and VEGFD. Angiogenic events are mediated via three VEGF receptors; mOMECs express all three VEGF receptors in vivo and in vitro. Exposure of mOMECs to VEGFC increased phosphorylation of AKT, while VEGFD treatment increased phosphorylation of both AKT and CREB. VEGFC and VEGFD increased mOMEC migration and the formation of endothelial cell sprouts in vitro. However, only VEGFD increased mOMEC proliferation. These findings suggest that VEGFC and VEGFD may work in conjunction with VEGFA to stimulate early events in angiogenesis of the primate ovulatory follicle.
authors.affiliation: National Creative Research Initiative Center for Multi-Dimensional Directed Nanoscale Assembly, Department of Materials Science and Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Soon Ok
authors.initials: SO
authors.lastname: Kim
authors.affiliation: Department of Genetics, Paul D. Coverdell Center, University of Georgia, 500 DW Brooks Drive, Athens, GA, USA.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Trau
authors.affiliation: Department of Physiological Sciences, Eastern Virginia Medical School; PO Box 1980, Norfolk, Virginia, USA.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Duffy
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008252:Macaca fascicularis / Q000502:physiology*; D018919:Neovascularization, Physiologic; D006080:Ovarian Follicle / Q000098:blood supply* / Q000502:physiology; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D033921:Vesicular Transport Proteins; D014841:von Willebrand Factor
keywords: endothelial cell; ovulation; macaque; ovary; vascular endothelial growth factor; FIGF