Rodent Models of Experimental Endometriosis: Identifying Mechanisms of Disease and Therapeutic Targets

Abstract

Background: Although it has been more than a century since endometriosis was initially described in the literature, understanding the etiology and natural history of the disease has been challenging. However, the broad utility of murine and rat models of experimental endometriosis has enabled the elucidation of a number of potentially targetable processes which may otherwise promote this disease.Objective: To review a variety of studies utilizing rodent models of endometriosis to illustrate their utility in examining mechanisms associated with development and progression of this disease.Results: Use of rodent models of endometriosis has provided a much broader understanding of the risk factors for the initial development of endometriosis, the cellular pathology of the disease and the identification of potential therapeutic targets.Conclusion: Although there are limitations with any animal model, the variety of experimental endometriosis models that have been developed has enabled investigation into numerous aspects of this disease. Thanks to these models, our under-standing of the early processes of disease development, the role of steroid responsiveness, inflammatory processes and the peritoneal environment has been advanced. More recent models have begun to shed light on how epigenetic alterations con-tribute to the molecular basis of this disease as well as the multiple comorbidities which plague many patients. Continued de-velopments of animal models which aid in unraveling the mechanisms of endometriosis development provide the best oppor-tunity to identify therapeutic strategies to prevent or regress this enigmatic disease.

Loss of MIG-6 results in endometrial progesterone resistance via ERBB2

“…We developed a mouse model of endometriosis based on Pgr cre/+ and mT/mG reporters that produces endometriotic lesions highly similar to those in humans. A mouse model in which excised human endometrial fragments are introduced into the peritoneum of immunocompromised mice is widely used, but is limited by lack of a normal immune system, which is thought to be important in endometriosis pathophysiology 44,45,46 . In contrast, the mouse model of induced endometriosis is a versatile model that has been used to study how the immune system 47 , hormones 48,49 and environmental factors 50, 51 affect endometriosis.…”

“…In contrast, the mouse model of induced endometriosis is a versatile model that has been used to study how the immune system 47 , hormones 48,49 and environmental factors 50, 51 affect endometriosis. The availability of a large number of transgenic mice in which speci c genes can be either eliminated or overexpressed make this induced endometriosis model ideal for studying speci c pathways in development and progression of endometriosis and other diseases 46 . However, current mouse models of endometriosis that involve ovariectomy and E2 treatment are impractical for studies of physiological functions that require natural uctuations in ovarian steroid hormones, such as fertility.…”

“…Because Mig-6 d/d mice have a fertility defect 20,32 , we applied a syngeneic mouse model to examine the effect of endometriotic lesions with Mig-6 ablation on the eutopic endometrium. Several groups have used syngeneic mouse models of endometriosis, in which the uterus of one mouse is removed, minced and injected intraperitoneally into recipient mice 46 . Syngeneic murine models have several potential advantages over the rodent surgical model: 1) peritoneal seeding of uterine fragments is more similar to retrograde menstruation in women; 2) either the donor or recipient animal can receive therapeutic intervention or be otherwise manipulated prior to induction of disease; and 3) a large number of transgenic mice in which speci c genes can be either eliminated or overexpressed are available.…”

Exploring the Modulatory Mechanism of Eleng Capsule in the Treatment of Endometriosis Based on Integrated Strategy of Transcriptomics Combined With Network Pharmacology

“…Endometriotic tissue is often induced in rodents via transplantation through surgery or intraperitoneal injection of uterine tissue fragments.The time of collection in rat models is 8 weeks after modeling; hence, the lesion has begun to undergo brosis. The interstitial space is a possible source of brotic cells during serosal in ammation and tissue repair.Therefore, it may play an important role in peritoneal brosis and adhesion formation [28]. Actin, a member of the ezrin-radixin-moesin family, plays a role in cell movement by linking the actin cytoskeleton.…”

In‑vitro models of human endometriosis (Review)

“…Based on this theory, a number of in-vitro and in-vivo models have been established to investigate the pathology behind endometriosis and its pathology. In animal models, the rhesus monkeys can develop endometriosis spontaneously, and endometriosis can be induced by transplanting endometrial tissues or cells from the same species or from humans into the peritoneum of primate or rodents, which has been reviewed in detail previously (5,6). Animal models are able to recapitulate the potential pathogenesis of human endometriosis in vivo.…”