Regulation of ovarian angiogenesis and function

哺乳动物卵巢是一个复杂的结构，具有独特的性质，因为它是成年人中经历周期性血管生成的少数结构之一。 血管生成是从现有血管系统形成新血管，并且作为促血管生成因子和抗血管生成因子之间平衡的结果而发生。迄今为止，一些促血管生成因子和抗血管生成因子的功能已在肿瘤血管中得到表征，但关于它们在卵巢中的功能的知识有限。 我的实验室在过去的5年里一直在评估这些因子在卵巢中的表达和功能。 我们的一个非常有趣和新颖的发现是，许多这些血管生成因子也表达在卵巢的血管外颗粒层。 我的研究项目的重点是评估这些血管生成因子的新血管外功能。 结合这种方法，我们还计划评估血管外和卵泡的后果，以建立抗血管生成疗法，通常用于治疗疾病，如癌症。 最后，我们计划评估从已知涉及卵巢功能障碍的生殖疾病患者收集的卵巢中血管生成因子的表达，以确定其潜在的参与。 由于促血管生成因子在卵巢中具有非常重要的血管和未知的血管外作用，因此直观地，通过抗血管生成疗法改变其表达将对卵巢血管生成和颗粒细胞功能具有显著影响。 抗血管生成治疗可能对个体的卵巢功能和生殖健康产生意想不到的影响，并且卵巢血管外隔室中血管因子表达的改变可能是各种生殖疾病病因学的重要组成部分。 该计划的结果将显着提高我们对调节卵巢健康和功能的因素的理解，也将继续致力于培养高素质的研究人员。

The mammalian ovary is a complex structure that has unique properties in that it is one of the few structures in the adult that undergoes cyclical angiogenesis. Angiogenesis is the formation of new blood vessels from existing vasculature and occurs as the result of a balance between pro- and anti-angiogenic factors. To date, the function of a number of pro- and anti-angiogenic factors have been characterized in tumour vessels, but limited knowledge is available regarding their function in the ovary. My laboratory has spent the past 5 years evaluating the expression and function of some of these factors in the ovary. One of our very interesting and novel findings is that many of these angiogenic factors are also expressed in the extravascular granulosa compartment of the ovary. The focus of my research program is to evaluate the novel extravascular functions of these angiogenic factors. In conjunction with this approach, we also plan to evaluate the extravascular and follicular consequences to established anti-angiogenic therapies that are often used to treat diseases such as cancer. Lastly, we plan to evaluate the expression of angiogenic factors in ovaries collected from individuals with reproductive disorders that are known to involve ovarian dysfunction to identify their potential involvement. As pro-angiogenic factors have very important vascular and unknown extravascular roles in the ovary, it is intuitive that alteration of their expression through anti-angiogenic therapies would have significant effects on ovarian angiogenesis and granulosa cell function. Anti-angiogenic treatments may have unanticipated effects on ovarian function and reproductive health of an individual and altered expression of vascular factors in the extravascular compartment of the ovary may be an important component in the etiology of various reproductive disorders. The results of this program will significantly improve our understanding of the factors that regulate ovarian health and function, and will also importantly continue our commitment to the training of highly-qualified researchers.