STEROID HORMONE REGULATION OF ANGIOGENESIS IN ENDOMETRIUM--IMPACT ON FERTILITY

子宫内膜经历广泛的细胞分化， 新血管的发育，即每次月经期间的血管生成 准备植入的周期。虽然雌激素和孕激素 在新生血管形成中的作用， 这一进程尚未确立。特异性促生长 肽类，即血管内皮生长/渗透因子（VEG/PF） 和碱性成纤维细胞生长因子（bFGF），刺激血管生成，在其他 系统.因此，本基础-临床联合研究项目 将在已建立的非人灵长类动物模型中利用体内方法， 狒狒，以及基于微载体的与人类共培养系统 子宫内膜细胞来检验雌激素和/或孕激素 通过刺激表达 VEGF/PR和bFGF及其受体。在研究1中，血管生成， 微血管通透性和表达及细胞定位 VEG/PF和bFGF以及它们各自的酪氨酸激酶受体将在本发明的一个实施方案中进行。 在狒狒正常月经周期期间和之后测定 卵巢切除术和急性或慢性给予雌二醇和/或 孕酮研究2将采用腺病毒介导的反义核酸， 寡核苷酸转移方法来破坏VEG/PF的表达， bFGF在子宫中的作用，以在体内测试这些肽具有 在子宫内膜内血管生成中起重要作用， 狒狒的生育能力。研究3将使用微载体 共培养系统，以测试雌激素和/或 孕酮通过调节人子宫内膜细胞血管生成 模拟VEG/PF和bFGF及其受体的表达。的 这项研究的目的是转移知识获得的 狒狒体内血管生成系统的生理学和调节 在体外研究人类子宫内膜细胞。完成本 项目将为提高我们的认识提供一个基础 的病因，并建立在未来的项目年更多 有效的激素治疗方式，不孕症的妇女。

The uterine endometrium undergoes extensive cellular differentiation and development of new blood vessels, i.e. angiogenesis during each menstrual cycle in preparation for implantation. Although estrogen and progesterone have established role in neovascularization, the mechanisms underlying this process have not been established. Specific growth-promoting peptides, i.e. vascular endothelial growth/permeability factor (VEG/PF) and basic fibroblast growth factor (bFGF), stimulate angiogenesis in other systems. Therefore, the present combined basic-clinical research project will utilize in vivo approaches in an established non-human primate model, the baboon, and a microcarrier-based cocultivation system with human endometrial cells to test the hypothesis that estrogen and/or progesterone regulate angiogenesis with the endometrium by stimulating expression of VEG/PR and bFGF and their receptors. In Study 1, angiogenesis, microvascular permeability and expression and cellular localization of VEG/PF and bFGF and their respective tyrosine kinase receptors will be determined in baboons during the normal menstrual cycle and after ovariectomy and the acute or chronic administration of estradiol and/or progesterone. Study 2 will employ an adenovirus-mediated antisense oligonucleotide transfer approach to disrupt the expression of VEG/PF and bFGF in the uterus to test in vivo the hypothesis that these peptides have essential roles upon angiogenesis within the endometrium and consequently upon fertility of the baboon. Study 3 will use a microcarrier cocultivation system to test the hypothesis that estrogen and/or progesterone regulate angiogenesis in human endometrial cells by simulating expression of VEG/PF and bFGF and their receptors. The objective of this study is to transfer the knowledge gained on the physiology and regulation of the angiogenesis system in vivo in the baboon to the study of human endometrial cells in vitro. Completion of this project will provide a fundamental basis for improving our understanding of the etiology of, and establishing in future project years more effective hormonal treatment modalities for, infertility in women.