Regulation of ovarian angiogenesis and function

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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. 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.