Expression and function of angiogenic factors in the ovary

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。卵巢是血管周期性形成、生长和消退的器官，是研究血管生成过程及其调控因素的良好工具。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。这些因子的血管外作用尚不清楚，本研究计划的目的是评估这些新功能。我们建议评估已知血管生成因子在卵巢中的血管外作用。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，除了抗血管生成治疗的血管外作用，我们还计划评估这些药物对卵巢血管的影响。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。因此，这些药物可能对个体的卵巢功能和生殖健康产生意想不到的影响。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.  As the ovary is an organ that has cyclical formation, growth, and regression of blood vessels, it is an excellent tool to study angiogenic processes and the factors that regulate them.  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 extravascular roles of these factors are not known and it is the intent of this research program to evaluate these novel functions.  We propose to evaluate the extravascular roles of known angiogenic factors in the ovary.  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, in addition to the extravascular roles of the anti-angiogenic treatments, we also plan to evaluate the effect of these agents on ovarian blood vessels.  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.  These agents, therefore, may have unanticipated effects on ovarian function and reproductive health of an individual.  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.