Dienogest exerts its anti-endometriotic effect throughthe direct suppression of matrix metallopeptidases

Dienogest exerts its anti-endometriotic effect throughthe direct suppression of matrix metallopeptidases | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Dienogest exerts its anti-endometriotic effect throughthe direct suppression of matrix metallopeptidases Hiroshi Honda, Norihisa Nishimichi, Michinori Yamashita, Yumiko Akimoto, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-84809/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Endometriosis, which affects up to 10% women of reproductive age, is defined by the presence of ectopic endometrial tissue outside the uterus. The current key drug of hormonal therapies for endometriosis is dienogest, which is a progestin with high specificity for the progesterone receptor. Although many findings about the anti-endometriotic effect of dienogest on endometriosis have been reported, the precise mechanisms of dienogest's anti-endometriotic effect remain unknown. Methods: To investigate the direct anti-endometriotic effect of dienogest on endometriotic cells, we determined and compared the genome-wide gene expression profiles of endometriotic stromal cells treated with dienogest (Dienogest group) and those not treated with dienogest (Control group) and then performed a pathway analysis using these data. To test the microarray data, we performed real-time RT-PCRs for matrix metallopeptidase (MMP)-1, MMP-3, MMP-10, and TIMP-4. Results: Six-hundred forty-seven genes were revealed to be differentially expressed between the Dienogest and Control groups. Of them, 314 genes were upregulated and 333 genes were downregulated in the Dienogest group compared to the Control group. We identified 20 canonical pathways that are significantly distinct in the Dienogest group versus the Control group. Among the 20 canonical pathways, MMPs including MMP-1, -3, and -10 were found to be the most involved genes. Conclusions: Our results suggest that dienogest may exert its anti-endometriotic effect through the direct suppression of MMPs. Sexual & Reproductive Medicine Endocrinology & Metabolism endometriosis dienogest microarray gene expression profile ingenuity pathways analysis MMP Figures Figure 1 Figure 2 Full Text Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-84809","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":2939040,"identity":"cc2cf8dd-2605-4a5f-91e6-57038be62471","order_by":0,"name":"Hiroshi Honda","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYBACAwYeIMnGIMfAwHwAWYKNoBZjIJGArJiwlsQGBh4DQuZDgDkD78HHBWV26X3nlyUw/qhgyOOXb2B78IGBLw+XFssGvmTjGeeSc2feeHyAmecMQ7FkGwO74QwGtmKcDrv/xkyat405d8ONYwnMjG3/EzccY2CT5mFgAzoVh5YDPCAt9ekGN84YMP5sY0jcD9Lyh7CWwwkG53sMGHiBWjawAbUw4NdibMxz7rjhzBtsCYeBfkmccSyxTbLHAI9fDvAYPuYpq5bnO3/44ENgiCX2Nx8+JvGj4hjOEEOAGwkMByAsRqCTDI4lENZy/gAKt4YILaNgFIyCUTBCAACL1VKHjvqGgwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-0943-6583","institution":"Hiroshima City Asa Hospital","correspondingAuthor":true,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Honda","suffix":""},{"id":2939041,"identity":"65526b23-9419-415e-8b58-06f92618c24c","order_by":1,"name":"Norihisa Nishimichi","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Norihisa","middleName":"","lastName":"Nishimichi","suffix":""},{"id":2939042,"identity":"cbe58bd4-41e6-4677-8d4a-61b26e4acd53","order_by":2,"name":"Michinori Yamashita","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Michinori","middleName":"","lastName":"Yamashita","suffix":""},{"id":2939043,"identity":"e1f0270f-1c6c-4014-9549-6388cecdf600","order_by":3,"name":"Yumiko Akimoto","email":"","orcid":"","institution":"Sumire Women's Clinic","correspondingAuthor":false,"prefix":"","firstName":"Yumiko","middleName":"","lastName":"Akimoto","suffix":""},{"id":2939044,"identity":"34ecc304-bb4e-4f62-88ff-68a2ebaaabf7","order_by":4,"name":"Hirotoshi Tanimoto","email":"","orcid":"","institution":"Sumire Women's Clinic","correspondingAuthor":false,"prefix":"","firstName":"Hirotoshi","middleName":"","lastName":"Tanimoto","suffix":""},{"id":2939045,"identity":"b2c443fe-0286-43b5-aeb7-71c191d78383","order_by":5,"name":"Mitsue Teramoto","email":"","orcid":"","institution":"Sera Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mitsue","middleName":"","lastName":"Teramoto","suffix":""},{"id":2939046,"identity":"9a0358d4-d707-432b-955e-36475fd91180","order_by":6,"name":"Hideki Teramoto","email":"","orcid":"","institution":"Sera Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hideki","middleName":"","lastName":"Teramoto","suffix":""},{"id":2939047,"identity":"31c7a3ab-30db-4b8b-9de6-74c350c0f0d2","order_by":7,"name":"Yasuyuki Yokosaki","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Yasuyuki","middleName":"","lastName":"Yokosaki","suffix":""}],"badges":[],"createdAt":"2020-09-28 15:17:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-84809/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-84809/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":2747847,"identity":"0f2949e9-bf86-4214-be77-e7527a7b6704","added_by":"auto","created_at":"2020-10-02 16:05:04","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106325,"visible":true,"origin":"","legend":"The top 10 canonical pathways that are significantly distinct in the Dienogest group compared to the Control group. The transverse line indicates the threshold of the distinct pathways in the Dienogest group under the condition of p\u003c0.05.","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-84809/v1/fig1.jpg"},{"id":2747849,"identity":"3832452b-b4ad-4e54-a17e-a1850dbd3ca0","added_by":"auto","created_at":"2020-10-02 16:05:04","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":44144,"visible":true,"origin":"","legend":"Validation of the microarray data and the pathway analysis by real-time RT-PCR. 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The current key drug of hormonal therapies for endometriosis is dienogest, which is a progestin with high specificity for the progesterone receptor. Although many findings about the anti-endometriotic effect of dienogest on endometriosis have been reported, the precise mechanisms of dienogest's anti-endometriotic effect remain unknown. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eTo investigate the direct anti-endometriotic effect of dienogest on endometriotic cells, we determined and compared the genome-wide gene expression profiles of endometriotic stromal cells treated with dienogest (Dienogest group) and those not treated with dienogest (Control group) and then performed a pathway analysis using these data. To test the microarray data, we performed real-time RT-PCRs for matrix metallopeptidase (MMP)-1, MMP-3, MMP-10, and TIMP-4.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Six-hundred forty-seven genes were revealed to be differentially expressed between the Dienogest and Control groups. Of them, 314 genes were upregulated and 333 genes were downregulated in the Dienogest group compared to the Control group. We identified 20 canonical pathways that are significantly distinct in the Dienogest group versus the Control group. Among the 20 canonical pathways, MMPs including MMP-1, -3, and -10 were found to be the most involved genes. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eOur results suggest that dienogest may exert its anti-endometriotic effect through the direct suppression of MMPs.\u003c/p\u003e","manuscriptTitle":"Dienogest exerts its anti-endometriotic effect throughthe direct suppression of matrix metallopeptidases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-10-02 16:05:02","doi":"10.21203/rs.3.rs-84809/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9d869e8f-4f6a-4ea3-9951-079d49c9fd28","owner":[],"postedDate":"October 2nd, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":668190,"name":"Sexual \u0026 Reproductive Medicine"},{"id":668191,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"2020-10-29T23:42:54+00:00","versionOfRecord":[],"versionCreatedAt":"2020-10-02 16:05:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-84809","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-84809","identity":"rs-84809","version":["v1"]},"buildId":"2u56kwukJI3zHK-uzyFNs","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}