Local delivery of angiopoietin-2 into the preovulatory follicle terminates the menstrual cycle in rhesus monkeys

Fuhua Xu, Richard L. Stouffer

    Research output: Contribution to journalArticle

    27 Scopus citations

    Abstract

    The angiopoietin (ANGPT)-receptor (TEK) system plays a crucial role in blood vessel formation and stability. Because the endogenous agonist ANGPT1, antagonist ANGPT2, and TEK are expressed in the primate ovary, experiments were designed to investigate their role at a critical time during tissue remodeling/ angiogenesis in the menstrual cycle (i.e., at midcycle during maturation, ovulation, and luteinization of the dominant follicle). Either vehicle, 20 μg of ANGPT1, 2 μg of ANGPT2 (low-dose), or 20 μg of ANGPT2 (high-dose) was injected directly into the preovulatory follicle of monkeys around the day (-1 to 0) of the midcycle estradiol (E2)/LH peak. Ovaries were evaluated on Day 3 postinjection for follicle rupture, and serum samples were analyzed for levels of E2 and progesterone. Similar to controls, ANGPT1 treatment was followed by ovulation, and elevated progesterone levels during the luteal phase. In contrast, high-dose ANGPT2 treatment prevented follicle rupture, and progesterone levels never rose above baseline in the subsequent 12 days. However, an E2 peak typically occurred 12 days postinjection. Laparoscopy detected a preovulatory follicle on the contralateral (noninjected) ovary. Progesterone levels subsequently increased above baseline in these animals. Thus, exogenous ANGPT2 disrupted maturation of the preovulatory follicle, preventing its ovulation and conversion into the corpus luteum. ANGPT antagonism eliminated the dominant structure, thereby resetting the ovarian cycle, with selection and maturation of the next preovulatory follicle occurring in a timely manner. The data are consistent with a critical role of the ANGPT-TIE1/TEK system in the ovary, notably at the late stages of follicle maturation during the menstrual cycle.

    Original languageEnglish (US)
    Pages (from-to)1352-1358
    Number of pages7
    JournalBiology of reproduction
    Volume72
    Issue number6
    DOIs
    StatePublished - Jun 2005

    Keywords

    • Angiogenesis
    • Angiopoietin-1
    • Angiopoietin-2
    • Corpus luteum
    • Follicle
    • Menstrual cycle
    • Ovary
    • Ovulation
    • Preovulatory follicle
    • Rhesus monkeys

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Cell Biology

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