The ovary is constantly remodeled by differentiation and involution of substructures. Recent results indicate a unique basis for interaction between parenchymal and other cells of the ovary and reveal novel mediators that appear to regulate the lysis and survival of ovarian structures. The hypothesis is that oxygen radicals serve as mediators of the selective lysis of ovarian structures, and that these reactive species play a fundamental role both in ovulation and in the oocyte. This novel proposition arose directly from recent findings that describe, for the first time, the unique and potent antigonadotropic and lytic actions of oxygen radicals in ovarian cells. Other evidence indicates that production of oxygen radicals, and defensive mechanisms against these reactive species, occurs in the ovary. Both of these processes appear to be under endocrine regulation by gonadotropins, and under paracrine control by cytokines, adenosine, and eicosanoids. The role of antioxidant vitamins (C, E and A), long known to be present in high levels in the ovary, is also predicted by this hypothesis. However, these important and novel aspects of ovarian regulation have not been investigated. This proposal is therefore focused on the identification of the cellular origin of oxygen radicals in the ovary, on their nature of action, and processes which regulate their production, action and degradation. Methods to be used will include cell culture, and in vivo studies, in addition to analysis of oxygen radicals, enzymes, and vitamins. Information gained from these studies has manifold benefits beyond the understanding of interactions between steroidogenic and other cells of the ovary. This information may reveal new insights into the etiology of infertility and open therapeutic avenues. An increased understanding of the etiology of ovarian cancer may also accrue since oxygen radicals are closely linked to carcinogenesis produced by uncontrolled production, by redox-cycling xenobiotics, or by inadequate defenses against these tumor promoters. Finally, we may gain a greater understanding of the role of antioxidant vitamins in reproduction and in immune cell processes in general.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Reproductive Biology Study Section (REB)
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Yale University
Schools of Medicine
New Haven
United States
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