MACROPHAGES, OXIDATION, AND ENDOMETRIOSIS

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Endometriosis is a common disorder that inflicts pain and suffering and is often the cause of infertility in women. There is a consensus that retrograde menstruation may account for the presence of endometrial cells in the peritoneal cavity. However, little is known regarding the etiology of the disease or why the disease occurs only in certain women despite the common occurrence of retrograde menstruation in most women. This program has five projects that propose novel hypotheses regarding the events that may lead to the establishment of endometriosis lesions. These ideas are extended as innovative specific aims that would be addressed using biochemical, immunological, and molecular biological techniques. Project 1 proposes that fundamental alterations in endometrial cell and macrophage scavenger functions to the peritoneal cavity of women with endometriosis are responsible for the survival and growth of the ectopic endometrium. Project 2 proposes an active mechanism by which intrinsic components of the peritoneal fluid may exacerbate an oxidative milieu that is conducive to the recruitment of mononuclear cells and the growth of the endometrial cells. This project suggests the presence of mildly oxidized lipoprotein components in the peritoneal fluid. Project 3 proposes that CSF-1 may play both autocrine and paracrine roles in promoting not only the growth of the endometrial cells but also in protecting macrophages from apoptotic death thereby increasing their survival in the peritoneal cavity. Project 4 will study the pharmacological regulation of macrophage scavenger function, production of cytokines, and endometrial cell growth. The effects of antioxidants, hormones, and retinoids on these functions will be determined. Project 5, the mini clinical project will establish the presence and differences in the markers of oxidative stress in the plasma of endometriosis subjects and controls. This project will also evaluate the efficacy of antioxidants to alter the levels of these markers. The program is supported by an administrative core and a tissue/cell culture core.