Intraovarian actions of anti-angiogenic agents disrupt periovulatory events during the menstrual cycle in monkeys

Fuhua Xu, Timothy M. Hazzard, Amanda Evans, Stephen Charnock-Jones, Stephen Smith, Richard L. Stouffer

    Research output: Contribution to journalReview article

    30 Scopus citations

    Abstract

    To determine if anti-angiogenic agents disrupt primate ovarian function, vehicle or a general angiostatic compound (TNP-470), specific antagonists of vascular endothelial growth factor (soluble VEGF receptor-1, sVEGFR-1; anti-VEGF monoclonal antibody, VEGF Ab) and/or an angiopoietin antagonist (Ang-2) were administered to rhesus monkeys: (1) locally via injection into the preovulatory follicle at midcycle or the developing corpus luteum at the midluteal phase; or (2) systemically via subcutaneous injection in the early follicular phase or at midcycle during the natural menstrual cycle. Compared to controls, intrafollicular injection of TNP-470 or sVEGFR-1 decreased circulating progesterone (P) levels in the subsequent luteal phase. Treatment with sVEGFR-1, but not TNP-470, also decreased the incidence of ovulation. Intrafollicular injection of Ang-2 also prevented ovulation, as well as any functional luteal phase. In the absence of elevated P, serum estradiol levels rose to peak levels 11-12 days post-Ang-2 treatment, at which time another large antral follicle was observed on the contralateral (noninjected) ovary. Intraluteal and systemic injection of VEGF antagonists alone or with Ang-2 had minimal effects. Thus, anti-angiogenic factors can act locally in the primate follicle to disrupt the gametogenic (oocyte release) and endocrine (steroid) functions of the ovary. However, further studies are needed to optimize delivery of angiogenic agents before they can be meaningfully evaluated as possible contraceptive agents.

    Original languageEnglish (US)
    Pages (from-to)239-248
    Number of pages10
    JournalContraception
    Volume71
    Issue number4
    DOIs
    StatePublished - Apr 2005

    Keywords

    • Angiopoietin-2
    • Corpus luteum function
    • Ovarian disruption
    • Ovulation
    • Rhesus monkeys
    • VEGF
    • Vascular endothelial growth factor

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynecology

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