The Lymphatic System in the Primate corpus Luteum

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DESCRIPTION (provided by applicant): The lymphatic system consists of thin-walled vessels and lymph nodes that collect protein-rich fluid (i.e. lymph) and return it to the blood stream. As a part of the circulatory system, the lymphatics are important for maintaining fluid balance and tissue homeostasis. Recent advances provided insight into the regulation and role of the lymphatics during embryogenesis and cancer metastasis, but there is little information on their development (lymphangiogenesis), maintenance, or destruction (lymphangiolysis) in healthy, adult tissues. The ovary should be an excellent organ for studying the physiology of the lymphatics, since the cyclic and temporary formation of gametogenic/endocrine tissues such as the corpus luteum (CL) is associated with remarkable changes in blood flow and vascular permeability. To date, there are no reports on the lymphatics in the primate CL. Such studies are needed since it is proposed that the extent and role of the lymphatics is positively correlated with CL size, i.e., the small CL of typical laboratory rodents is virtually devoid of lymphatics. Therefore, studies are proposed to test the hypothesis that the lymphatic system exists in the primate CL and that CL development is associated with lymphangiogenesis. Using the rhesus monkey as a primate model, studies were designed: (a) Aim No.1 - To investigate the presence, localization, and dynamics of lymphatic vessels in the primate ovary, specifically in the CL throughout the luteal lifespan of the menstrual cycle. Newly - discovered markers for lymphatic endothelial cells (LECs), e.g., PROX-1, LYVE-1, podoplanin, and VEGFR-3, will be validated by immunocytochemistry, and the numbers of LECs and lymphatic area quantitated by image analysis; (b) Aim No.2 - To analyze the expression of novel lymphangiogenic factors, vascular endothelial growth factor (VEGF)-C and -D, and their receptor VEGFR-3 in the primate CL. Real time PCR and western blotting, plus in situ hybridization and immunocytochemistry will be employed to quantitate mRNA and protein expression, plus localize expression to specific cell types in the ovary/CL during the menstrual cycle. This knowledge will contribute to our understanding of the structure-function of the primate CL, and should provide a solid rationale for further studies on the regulation and role of the lymphatic system in the primate ovary during the normal menstrual cycle and in ovarian disorders, such as ovarian hyperstimulation syndrome or ovarian cysts.