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.

Involvement of 17β-hydroxysteroid dehydrogenase type gene 1 937 A>G polymorphism in infertility in Polish Caucasian women with endometriosis

“…However, abnormal production of estrogen contributes to various estrogen-related diseases including endometriosis [ 19 , 20 ]. The significant function of E2 in the development of this disease has been well documented in animal models including rodent and baboon models [ 21 , 22 ]. More endometriotic lesions were developed in E2-treated mice than control animals [ 21 ].…”

“…More endometriotic lesions were developed in E2-treated mice than control animals [ 21 ]. Recently, Nair et al employed antiprogestin treatment which resulted in unopposed estrogenicity and development of spontaneous endometriosis in baboons [ 22 ].…”

WITHDRAWN: Endometriosis related sex steroid hormones, hypothalamic pituitary gonadal axis hormones and related animal modeling: A comprehensive review of published articles and endometriosis induction methods from 2010 to 2021 with scoring based approach

“…Therefore, they supplemented EC304 with progesterone treatment, which lead to multifocal stacks of differentiated endometrial glands and stroma on the surface of the uterus and peritoneal cavity. Administration of EC304 and progesterone clearly increased the expression of ERα as the direct hallmark of estrogenicity in the endometrial tissue (115).…”

New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity

“…Progesterone is the ligand of the progesterone receptor (PR) and it is known to trigger RANK expression, which enhances the proliferation of different cells such as osteoclasts and epithelial breast cells. In this way, the therapy based on the administration of the agonistic ligands of the sex hormone receptors leads to different strong and serious sides effects [18][19][20][21][22][23][24]. A new class of compounds which would be used as anti-RANK agents are selective progesterone modulators -mesoprogestins and antiprogestins.…”