Expression and function of angiogenic factors in the ovary

哺乳动物卵巢是一种复杂的结构，具有独特的性质，因为它是成体中为数不多的经历周期性血管生成的结构之一。血管生成是从现有的血管形成新的血管，是促血管生成因子和抗血管生成因子之间平衡的结果。由于卵巢是一个具有周期性血管形成、生长和退化的器官，因此它是研究血管生成过程和调节它们的因素的极好工具。迄今为止，许多促血管生成因子和抗血管生成因子的功能在肿瘤血管中得到了表征。但对它们在卵巢中的功能了解有限。在过去的5年里，我的实验室一直在评估其中一些因子在卵巢中的表达和功能。我们非常有趣和新颖的发现之一是，许多血管生成因子也在卵巢的血管外颗粒间表达。这些因子的血管外作用尚不清楚，本研究计划旨在评估这些新功能。我们建议评估已知的血管生成因子在卵巢中的血管外作用。结合这一方法，我们还计划评估通常用于治疗癌症等疾病的抗血管生成疗法对血管外和卵泡的影响。最后，除了抗血管生成疗法的血管外作用外，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外作用和未知的血管外作用，因此通过抗血管生成疗法改变它们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，可能会对个人的卵巢功能和生殖健康产生意想不到的影响。该项目的结果将显著提高我们对调节卵巢健康和功能的因素的了解，也将重要地继续我们对高素质研究人员培训的承诺。

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.