RETINOID EFFECTS ON INFLAMMATION AND CELL GROWTH ASSOCIATED WITH ENDOMETRIOSIS. Retinoids are essential to the differentiation and development of reproductive tissue, including that from the endometrium and ovaries. In portions of the parent grant relating to this administrative supplement application, we hypothesized that 1) retinoid metabolism and signaling are dysregulated in the reproductive tissue of women with endometriosis; 2) the immunologic effects of retinoids differ in women with and without endometriosis, accounting for some of the pathophysiologic manifestations of this disease including pelvic pain and sub-fertility; and 3) the effects of retinoids on human reproduction are significant and might be exploited to improve fertility outcomes in all women including those suffering from endometriosis. To address these hypotheses, we have pursued mechanistic studies regarding retinoid effects on the monocyte/macrophage CD36 scavenger receptor and vascular endothelial growth factor (VEGF) gene expression in endometrial cells (Aim 2). In addition, we have quantified retinoid levels in reproductive tissues of human subjects with and without endometriosis (Aim 1). As part of this study, we have determined that human follicular fluid obtained during IVF oocyte retrieval from endometriosis and control subjects also contains quantifiable retinoid levels and that these levels do not parallel serum levels (suggesting intraovarian retinoid metabolism). It is our belief that ovarian retinoids, and follicular fluid retinoids in particular, play important roles in fertility; perturbations of which may explain impaired embryo quality and endometrial receptivity observed in women with endometriosis. Supporting this, we have found in pilot studies that follicular fluid retinoid levels seem to correlate with embryo grade when the respective oocytes are fertilized and followed in IVF cycles. Thus, retinoids are candidate markers for embryo quality and represent potential therapeutic targets for infertile endometriosis patients. This supplement proposes to accelerate the pace of discovery with regards to the hypotheses listed above. This support permits the hiring of a new post-doctoral fellow to evaluate an expanded list of retinoid metabolites and expedite molecular studies on the immune effects of retinoids; the hiring of a new research nurse to manage specimen procurement, data extraction, and clinical correlations with data obtained; and supports the additional effort of a study embryologist who will increase the consistency and accelerate the acquisition of ovarian tissues obtained from IVF retrievals. With these added resources, rapid and significant distinctions can be made regarding retinoid levels, immune function, pelvic pain, and reproductive performance in women with and without endometriosis.