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，因为它是成人中为数不多的经历周期性血管生成的结构之一。血管生成是由现有血管系统形成的新血管，是促血管生成因子和抗血管生成因子平衡的结果。迄今为止，许多促血管生成因子和抗血管生成因子的功能已经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年里一直在评估卵巢中这些因子的表达和功能。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在卵巢的血管外颗粒室中表达。我的研究计划的重点是评估这些血管生成因子的新的血管外功能。结合这种方法，我们还计划评估已建立的抗血管生成疗法对血管外和滤泡的影响，这些疗法通常用于治疗癌症等疾病。最后，我们计划评估从已知涉及卵巢功能障碍的生殖障碍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，因此通过抗血管生成治疗改变促血管生成因子的表达将对卵巢血管生成和颗粒细胞功能产生显著影响。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，卵巢血管外腔室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。这个项目的结果将大大提高我们对调节卵巢健康和功能的因素的理解，也将重要地继续我们对培养高素质研究人员的承诺。

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.