title: An efficient model of human endometriosis by induced unopposed estrogenicity in baboons.
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.
authors.affiliation: Evestra, Inc., San Antonio, TX, USA.
authors.forename: Hareesh B
authors.initials: HB
authors.lastname: Nair
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Baker
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Owston
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Escalona
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dick
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: VandeBerg
authors.affiliation: Evestra, Inc., San Antonio, TX, USA.
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Nickisch
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004715:Endometriosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D010215:Papio; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*
chemical_list: D004967:Estrogens; D011980:Receptors, Progesterone
keywords: Pathology Section; attachment; baboon; endometrial stromal cells; endometriosis; invasion