VASOACTIVE FACTORS IN MENSTRUAL CYCLES & OVARIAN HYPERSTIMULATION SYNDROME

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 这项研究的目标是了解促进形成和功能的特定分子的作用（即，血管生成因子）或变性（即，血管溶解因子）的卵巢血管，因此在灵长类动物的排卵卵泡和黄体的结构功能。 最近的发现表明，参与胚胎血管发生的因素存在于卵巢中，例如，血管内皮生长因子（VEGF）、血管生成素（ANGPT）和促动素原（PK）家族的成员。 目前正在恒河猴中进行研究，并在人类细胞上进行相关实验，以检验以下假设：（a）血管生成和血管生成之间的平衡（VEGF-A，ANGPT-1）和血管溶解ANGPT-2，可溶性VEGF受体）因子影响卵泡和黄体中血管的成熟和功能;（B）最近发现的因子，称为内分泌腺（EG）-VEGF或PK 1，补充VEGF-A在灵长类动物卵巢中的作用;和（c）在不孕症方案中的控制性卵巢刺激周期期间，VEGF、ANGPT或PK的过度或异常产生/作用发生，并引起卵巢过度刺激综合征。 将在卵巢组织和血液样本中分析血管生成和血管溶解因子及其受体的基因和蛋白表达。 将对猴给予血管生成和血管溶解因子或其拮抗剂，并检查对卵巢血管、卵泡和黄体结构-功能的影响。在本年度，非侵入性的方法，使用三维，对比增强超声和磁共振成像的实时分析卵巢血流，体积和渗透性的发展。

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.