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PARENT SESSION
PLATFORM SESSION 9: VASCULAR AND INTRACELLULAR SIGNALS IN CORPUS LUTEUM
Chair: Davis, John1, 1
Co-chair: Valdezk, Kelli1, 1
Grand Ballroom V
2:00 PM-4:00 PM

(208) NEUROPILIN-1 AND -2 EXPRESSION IN THE MONKEY CORPUS LUTEUM DURING THE MENSTRUAL CYCLE.

Xu, Fuhua1, Hazzard, Timothy1, Scheffler, Larry1, Stouffer, Richard1,2, 1 Division of Reproductive Sciences, Beaverton, OR2 Department of Physiology and Pharmacology, Portland, OR

ABSTRACT- Recent evidence indicates that neuropilins (NPs) not only act as collapsin/semaphorin receptors to control neuronal growth, but also bind certain isoforms of vascular endothelial growth factor (e.g., VEGF165) and enhance VEGF-receptor interaction and angiogenesis. We previously detected NP-1 mRNA in the monkey ovary using RT-PCR techniques. As an initial step in considering NP's role in VEGF-regulated angiogenesis in the primate corpus luteum (CL), experiments were designed to quantitate NP-1 and -2 mRNA and to localize NP proteins in the macaque CL at specific stages during the luteal lifespan in the natural menstrual cycle. The CL (n=3/stage) was collected from rhesus monkeys in the early (3-5 days post LH surge), mid (6-8 days), mid-late (10-12 days) and late (14-16 days) luteal phase, and at menstruation (17-18 days). Tissues were bisected and used to measure NP mRNAs by real-time PCR and to visualize NP proteins by immunohistochemistry. The level of NP-1 mRNA (relative to control 18sRNA) was highest in the early and mid-late luteal phase, before declining 4.2-fold (p<0.05) by late luteal phase and menstruation. Intense staining, in the presence of anti-human NP-1 antibody, but not in controls (NP-1 antibody plus inhibitor peptide, Zymed laboratories Inc.), was observed in the developing microvasculature during the early luteal phase and in large vessels by mid luteal phase. NP-2 mRNA was detectable in the macaque CL, but levels did not change significantly throughout the luteal phase. In contrast to NP-1, specific staining in the presence of anti-human NP-2 antibody was observed in luteal cells as well as in vessels, but not in the surrounding stromal cells. These data indicate that both NP-1 and NP-2 are expressed in the monkey CL throughout the menstrual cycle. Localization to vascular cells is consistent with a possible role of NP-1 and -2 as coreceptors for VEGF and enhancers of VEGF action/angiogenesis during development and maintenance of the primate CL. However, NP actions in luteal cells may also exist. Supported by NIH/NICHD U54 HD18185, HD22408, WHO/Rockefeller Foundation (RF96020) and NCRR RR00163.

KEY WORDS: Rhesus monkey, Corpus luteum, Angiogenesis, Neuropilin


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