A mouse model of endometriosis that displays vaginal, colon, cutaneous, and bladder sensory comorbidities

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dc.contributor.authorCastro, J.
dc.contributor.authorMaddern, J.
dc.contributor.authorGrundy, L.
dc.contributor.authorManavis, J.
dc.contributor.authorHarrington, A.M.
dc.contributor.authorSchober, G.
dc.contributor.authorBrierley, S.M.
dc.date.issued2021
dc.description.abstractEndometriosis is a painful inflammatory disorder affecting ~10% of women of reproductive age. Although chronic pelvic pain (CPP) remains the main symptom of endometriosis patients, adequate treatments for CPP are lacking. Animal models that recapitulate the features and symptoms experienced by women with endometriosis are essential for investigating the etiology of endometriosis, as well as developing new treatments. In this study, we used an autologous mouse model of endometriosis to examine a combination of disease features and symptoms including: a 10 week time course of endometriotic lesion development; the chronic inflammatory environment and development of neuroangiogenesis within lesions; sensory hypersensitivity and altered pain responses to vaginal, colon, bladder, and skin stimulation in conscious animals; and spontaneous animal behavior. We found significant increases in lesion size from week 6 posttransplant. Lesions displayed endometrial glands, stroma, and underwent neuroangiogenesis. Additionally, peritoneal fluid of mice with endometriosis contained known inflammatory mediators and angiogenic factors. Compared to Sham, mice with endometriosis displayed: enhanced sensitivity to pain evoked by (i) vaginal and (ii) colorectal distension, (iii) altered bladder function and increased sensitivity to cutaneous (iv) thermal and (v) mechanical stimuli. The development of endometriosis had no effect on spontaneous behavior. This study describes a comprehensive characterization of a mouse model of endometriosis, recapitulating the clinical features and symptoms experienced by women with endometriosis. Moreover, it delivers the groundwork to investigate the etiology of endometriosis and provides a platform for the development of therapeutical interventions to manage endometriosis-associated CPP.
dc.description.statementofresponsibilityJoel Castro, Jessica Maddern, Luke Grundy, Jim Manavis, Andrea M. Harrington, Gudrun Schober, Stuart M. Brierley
dc.identifier.citationThe FASEB Journal, 2021; 35(4):1-20
dc.identifier.doi10.1096/fj.202002441R
dc.identifier.issn0892-6638
dc.identifier.issn1530-6860
dc.identifier.orcidCastro, J. [0000-0002-5781-2224]
dc.identifier.orcidManavis, J. [0000-0001-7381-7781] [0000-0003-1268-561X]
dc.identifier.orcidHarrington, A.M. [0000-0002-1562-4137]
dc.identifier.orcidBrierley, S.M. [0000-0002-2527-2905]
dc.identifier.urihttp://hdl.handle.net/2440/130423
dc.language.isoen
dc.publisherFederation of American Society of Experimental Biology
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1181448
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/P1126378
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1139366
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1140297
dc.relation.granthttp://purl.org/au-research/grants/arc/DE130100223
dc.relation.granthttp://purl.org/au-research/grants/arc/DP180101395
dc.rights© 2021 Federation of American Societies for Experimental Biology
dc.source.urihttps://doi.org/10.1096/fj.202002441r
dc.subjectbladder dysfunction
dc.subjectcolonic hypersensitivity
dc.subjectcutaneous mechanical and thermal hypersensitivity
dc.subjectendometriotic lesions
dc.subjectvaginal hypersensitivity
dc.titleA mouse model of endometriosis that displays vaginal, colon, cutaneous, and bladder sensory comorbidities
dc.typeJournal article
pubs.publication-statusPublished

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