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(20) LOCAL DELIVERY OF ANGIOPOIETIN-2 INTO THE PREOVULATORY FOLLICLE TERMINATES THE MENSTRUAL CYCLE IN RHESUS MONKEYS. Xu, Fuhua1, Stouffer, Richard1, 2, 3, 1 Devision of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR2 Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR3 Department of Environmental & Biomolecular Systems, OGI School of Science & Engineering, Beaverton, OR ABSTRACT- Recent studies indicate that the angiopoietin (Ang)-receptor (Tie-2) system plays a crucial role in blood vessel formation, with endogenous Ang-1 promoting vessel maturation and stability, and endogenous Ang-2 antagonizing this action to cause vessel instability. Since Ang-1, -2 and Tie-2 are expressed in the primate follicle/corpus luteum, experiments were designed to investigate their role at a critical time during tissue remodeling/angiogenesis in the ovarian cycle, i.e. at midcycle during final maturation, ovulation and luteinization of the dominant follicle. Either vehicle, or 20 KEY WORDS: Angiogenesis, Rhesus Monkey, Angiopoietin, Preovulatory Follicle |
g of Ang-1 or Ang-2 (n≥3/treatment) was injected directly into the preovulatory follicle of rhesus monkeys around the day (-1 to 0) of the midcycle estradiol (E)/LH peak. Ovaries were viewed on day 3 post-injection for evidence of follicle rupture, and daily serum samples were analyzed for E and progesterone (P) levels. Similar to controls, Ang-1 treatment was followed by follicle rupture, and elevated P levels (peak=3.0±1.2ng/ml) during a two-week luteal phase. In contract, Ang-2 treatment resulted in the absence of follicle rupture, and P levels that never rose of baseline (0.2±0.1ng/ml) in the subsequent 12 days. However, an E peak (418±193pg/ml) typically (4 of 5 animals) occurred 12±0.7 days post- injection. Laparoscopy detected a preovulatory follicle on the contralateral (non-injected) ovary. P levels subsequently increased above baseline in these animals. Thus, acute exposure to exogenous Ang-2 disrupted maturation of the preovulatory follicle, preventing its ovulation and conversion into the corpus luteum. The data suggest that Ang-2 can eliminate the dominant structure, thereby resetting the ovarian cycle, with selection and maturation of the next preovulatory follicle occurring in a timely manner. This study provides the first evidence for a critical role of the Ang-Tie system in the primate ovary, notably in the later stages of follicle maturation. Supported by: RF96020, HD18185, and RR00163.