Expression and function of angiogenic factors in the ovary

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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.