VASOACTIVE FACTORS IN MENSTRUAL CYCLES & OVARIAN HYPERSTIMULATION SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 除了病理和创伤情况外，成人的血管发育和退化通常局限于卵巢和女性生殖道，即在月经周期中经历周期性生长和退化的组织。本研究的目的是了解促进卵巢血管的形成和功能(即血管生成因子)或退化(即血管溶解因子)的特定分子的作用，从而促进灵长类动物排卵卵泡和黄体的结构和功能。最近的发现表明，参与胚胎血管生成的因子存在于卵巢中，如血管内皮生长因子(VEGF)、血管生成素(ANGPT)和原激动素(PK)家族的成员。恒河猴正在进行研究，并进行了相关的人体细胞实验，以检验如下假设：(A)血管生成因子(VEGF-A，ANGPT-1)和血管溶解因子(ANGPT-2，可溶性血管内皮生长因子受体)之间的平衡影响卵泡和黄体中血管的成熟和功能；(B)最近发现的内分泌腺因子(EG)-VEGF或PK1在灵长类卵巢中补充了VEGF-A的作用；以及(C)在不孕症的受控卵巢刺激周期中，VEGF、ANGPT或PK的过度或异常产生/作用，并导致卵巢过度刺激综合征。血管生成和血管溶解因子及其受体的基因和蛋白表达将在卵巢组织和血液样本中进行分析。将血管生成和血管溶解因子或其拮抗剂应用于猴子，并观察其对卵巢血管、卵泡和黄体结构和功能的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aside from pathologic and trauma conditions, blood vessel development and degeneration in adults is generally limited to the ovary and female reproductive tract, i.e., tissues that undergo cyclic growth and regression during the menstrual cycle. 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.