An efficient model of human endometriosis by induced unopposed estrogenicity in baboons

Hareesh B. Nair, Robert Baker, Michael A. Owston, Renee Escalona, Edward J. Dick, John L. VandeBerg, Klaus J. Nickisch

    Research output: Contribution to journalArticlepeer-review

    6 Scopus citations

    Abstract

    Endometriosis is a chronic estrogen-dependent disease that occurs in approximately 10% of reproductive age women. Baboons offer a clear benefit for studying the initiation and progression of endometriosis since baboon is very close to humans phylogenetically. Progestins are used in the treatment of endometriosis. The therapeutic window of progestins depends on the ratio of its affinity towards progesterone receptor agonism verses antagonism. The present study is to determine the role of pure antiprogestin in baboon endometriosis. We hypothesize that pure antiprogestin will induce unopposed estrogenicity and spontaneous endometriosis in baboons. The rate of endometrial invasion and attachment through modeled peritoneum in the presence and absence of progesterone and antiprogestin was evaluated in this study. A baboon model of endometriosis induced by unopposed estrogenicity using progesterone receptor antagonist (EC304) was used in this study. We observed EC304 has induced unopposed estrogenicity that deregulated proteins involved in attachment, invasion, cell growth, and steroid hormone receptors in this model. Our data suggest that depleting progesterone levels in the endometrium will increase estrogen hyper-responsiveness that leads to increased endometriotic lesion progression in the baboon (Papio anubis) model. This study reports a refined model of human endometriosis in baboons that could potentially be used to develop new diagnostic and therapeutic strategies for the benefit of women suffering from endometriosis.

    Original languageEnglish (US)
    Pages (from-to)10857-10869
    Number of pages13
    JournalOncotarget
    Volume7
    Issue number10
    DOIs
    StatePublished - 2016

    Keywords

    • Attachment
    • Baboon
    • Endometrial stromal cells
    • Endometriosis
    • Invasion
    • Pathology section
    • Unopposed estrogenicity

    ASJC Scopus subject areas

    • Oncology

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