Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease

Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease | 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 Article Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease Bo Yu, Stephen McCartney, Susan Strenk, Daniel J. Valint, Congzhou Liu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2891189/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Sep, 2023 Read the published version in Reproductive Sciences → Version 1 posted 4 You are reading this latest preprint version Abstract Objective: To facilitate in vitro mechanistic studies in pelvic inflammatory disease (PID) and subsequent tubal factor infertility, as well as ovarian carcinogenesis, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. Design: Experimental study. Setting: Academic medical and researchcenter. Patients: FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. Interventions: We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhesseavaginae . Main Outcome Measures: The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Results: Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae . Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in F. vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. Conclusion : Patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful model system to study the host-pathogen interaction during bacterial infection which may facilitate mechanistic investigations in PID and its contribution to tubal factor infertility and ovarian carcinogenesis. Fallopian tube organoids pelvic inflammatory disease (PID) tubal factor infertility vaginal bacteria host-pathogen interaction Full Text Cite Share Download PDF Status: Published Journal Publication published 19 Sep, 2023 Read the published version in Reproductive Sciences → Version 1 posted Reviewers agreed at journal 06 Jun, 2023 Reviewers invited by journal 19 May, 2023 Editor assigned by journal 05 May, 2023 First submitted to journal 03 May, 2023 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-2891189","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":202129511,"identity":"749dbd6d-b481-4bc6-a4c2-21a703abc6a8","order_by":0,"name":"Bo Yu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYBACAyA+8AHEYj7AwMDDwMDYQIQWxoMzQBRbAvFamA/zkKTFXCLH4LDNnz/y5mzMxz68YbCR3XCAgBbLGUAtuW0Ghjvb2JJnzmFIMyaoxeAGSEuDAeOG+z3GzDwMhxOJ02Lxx8B+wzEekJb/RGphYDNIhGo5QFiLZc+zgoO9bcbJG46xJTPOMUg2nklIizl78uYPP/7I2W44xnyY4U2FnWwfIS0MAgko7iSkHAT4CRo6CkbBKBgFIx4AAO35RetgwApWAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-6051-077X","institution":"Stanford University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Bo","middleName":"","lastName":"Yu","suffix":""},{"id":202129512,"identity":"4824353e-860b-48b7-9b77-60bbfc7e91e0","order_by":1,"name":"Stephen McCartney","email":"","orcid":"","institution":"University of Washington","correspondingAuthor":false,"prefix":"","firstName":"Stephen","middleName":"","lastName":"McCartney","suffix":""},{"id":202129513,"identity":"158404a9-951f-4f05-9550-23325d9aa402","order_by":2,"name":"Susan Strenk","email":"","orcid":"","institution":"Fred Hutchinson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Susan","middleName":"","lastName":"Strenk","suffix":""},{"id":202129514,"identity":"75f6ee45-34c6-4936-bc35-13c448162b5a","order_by":3,"name":"Daniel J. 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Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Fallopian tube organoids, pelvic inflammatory disease (PID), tubal factor infertility,\tvaginal bacteria, host-pathogen interaction","lastPublishedDoi":"10.21203/rs.3.rs-2891189/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2891189/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTo facilitate \u003cem\u003ein vitro \u003c/em\u003emechanistic studies in pelvic inflammatory disease (PID) and subsequent tubal factor infertility, as well as ovarian carcinogenesis, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign: \u003c/strong\u003eExperimental study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSetting: \u003c/strong\u003eAcademic medical and researchcenter.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients: \u003c/strong\u003eFT tissues were obtained from four patients after salpingectomy for benign gynecological diseases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions: \u003c/strong\u003eWe introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, \u003cem\u003eLactobacillus crispatus \u003c/em\u003eand \u003cem\u003eFannyhesseavaginae\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMain Outcome Measures: \u003c/strong\u003eThe inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eCompared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the \u003cem\u003eLactobacillus crispatus \u003c/em\u003einfected organoids and those infected by \u003cem\u003eFannyhessea vaginae\u003c/em\u003e. Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in \u003cem\u003eF. vaginae \u003c/em\u003einfected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful model system to study the host-pathogen interaction during bacterial infection which may facilitate mechanistic investigations in PID and its contribution to tubal factor infertility and ovarian carcinogenesis.\u003c/p\u003e","manuscriptTitle":"Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-05-23 16:37:13","doi":"10.21203/rs.3.rs-2891189/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2023-06-06T06:22:15+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-05-19T18:28:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-05-05T11:39:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Reproductive Sciences","date":"2023-05-03T15:44:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"reproductive-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"resc","sideBox":"Learn more about [Reproductive Sciences](https://rd.springer.com/journal/43032)","snPcode":"43032","submissionUrl":"https://www.editorialmanager.com/resc/default2.aspx","title":"Reproductive Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"98691fbd-e094-4341-8d41-ace5aa3a2bb0","owner":[],"postedDate":"May 23rd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-09-25T15:03:31+00:00","versionOfRecord":{"articleIdentity":"rs-2891189","link":"https://doi.org/10.1007/s43032-023-01350-5","journal":{"identity":"reproductive-sciences","isVorOnly":false,"title":"Reproductive Sciences"},"publishedOn":"2023-09-19 15:00:43","publishedOnDateReadable":"September 19th, 2023"},"versionCreatedAt":"2023-05-23 16:37:13","video":"","vorDoi":"10.1007/s43032-023-01350-5","vorDoiUrl":"https://doi.org/10.1007/s43032-023-01350-5","workflowStages":[]},"version":"v1","identity":"rs-2891189","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2891189","identity":"rs-2891189","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}