This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this research is to understand the role of specific molecules that promote the formation and function (i.e., angiogenic factors) or degeneration (i.e., angiolytic factors) of ovarian vessels, and hence the structure-function of the ovulatory follicle and corpus luteum in primates. Recent discoveries suggest that factors involved in vasculogenesis in the embryo are present in the ovary, e.g., members of the vascular endothelial growth factor (VEGF), angiopoietin (ANGPT) and prokineticin (PK) families. Studies are ongoing in the rhesus monkey, with correlate experiments on human cells, to test the hypothesis that: (a) the balance between angiogenic (VEGF-A, ANGPT-1) and angiolytic (ANGPT-2, soluble VEGF receptor) factors influences the maturity and function of vessels in the follicle and corpus luteum;(b) the recently discovered factor, termed endocrine gland (EG)-VEGF or PK1 complements the actions of VEGF-A in the primate ovary;and (c) excessive or aberrant production/action of VEGF, ANGPT or PK occurs during controlled ovarian stimulation cycles in infertility protocols, and causes ovarian hyperstimulation syndrome. Gene and protein expression for angiogenic and angiolytic factors, and their receptors, will be analyzed in ovarian tissues and blood samples. Angiogenic and angiolytic factors or their antagonists will be administered to monkeys and effects on the structure-function of ovarian blood vessels, follicles and corpora lutea will be examined. In the current year, non-invasive methods using 3-dimentional, contrast-enhanced ultra sonography and magnetic resonance imaging were developed for real-time analyses of ovarian blood flow, volume and permeability.
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