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dc.contributor.authorOliver, Elizabeth
dc.contributor.authorAlves-Lopes, João Pedro
dc.contributor.authorHarteveld, Femke
dc.contributor.authorMitchell, Rod T
dc.contributor.authorÅkesson, Elisabet
dc.contributor.authorSöder, Olle
dc.contributor.authorStukenborg, Jan-Bernd
dc.date.accessioned2021-11-25T17:29:32Z
dc.date.available2021-11-25T17:29:32Z
dc.date.issued2021-09-23
dc.identifier.issn1741-7007
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331194
dc.description.abstractBACKGROUND: Advances in three-dimensional culture technologies have led to progression in systems used to model the gonadal microenvironment in vitro. Despite demonstrating basic functionality, tissue organisation is often limited. We have previously detailed a three-dimensional culture model termed the three-layer gradient system to generate rat testicular organoids in vitro. Here we extend the model to human first-trimester embryonic gonadal tissue. RESULTS: Testicular cell suspensions reorganised into testis-like organoids with distinct seminiferous-like cords situated within an interstitial environment after 7 days. In contrast, tissue reorganisation failed to occur when mesonephros, which promotes testicular development in vivo, was included in the tissue digest. Organoids generated from dissociated female gonad cell suspensions formed loosely organised cords after 7 days. In addition to displaying testis-specific architecture, testis-like organoids demonstrated evidence of somatic cell differentiation. Within the 3-LGS, we observed the onset of AMH expression in the cytoplasm of SOX9-positive Sertoli cells within reorganised testicular cords. Leydig cell differentiation and onset of steroidogenic capacity was also revealed in the 3-LGS through the expression of key steroidogenic enzymes StAR and CYP17A1 within the interstitial compartment. While the 3-LGS generates a somatic cell environment capable of supporting germ cell survival in ovarian organoids germ cell loss was observed in testicular organoids. CONCLUSION: The 3-LGS can be used to generate organised whole gonadal organoids within 7 days. The 3-LGS brings a new opportunity to explore gonadal organogenesis and contributes to the development of more complex in vitro models in the field of developmental and regenerative medicine.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleSelf-organising human gonads generated by a Matrigel-based gradient system.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2021
prism.publicationNameBMC Biol
prism.startingPage212
prism.volume19
dc.identifier.doi10.17863/CAM.78641
dc.identifier.doi10.17863/CAM.78641
dcterms.dateAccepted2021-09-09
rioxxterms.versionofrecord10.1186/s12915-021-01149-3
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-09-23
dc.contributor.orcidStukenborg, Jan-Bernd [0000-0002-2839-1870]
dc.identifier.eissn1741-7007
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-09-23


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International