title: Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.
abstract: In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.|Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Margherita Y
authors.initials: MY
authors.lastname: Turco
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.|Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Gardner
authors.affiliation: Department of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2SP, UK.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Hughes
authors.affiliation: Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Tereza
authors.initials: T
authors.lastname: Cindrova-Davies
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gomez
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.|Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Lydia
authors.initials: L
authors.lastname: Farrell
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Hollinshead
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, London, NW3 2QU, UK.
authors.forename: Steven G E
authors.initials: SGE
authors.lastname: Marsh
authors.affiliation: Division of Reproductive Health, Clinical Science Research Laboratories, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Jan J
authors.identifier: http://orcid.org/0000-0003-0116-9329
authors.initials: JJ
authors.lastname: Brosens
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Hilary O
authors.initials: HO
authors.lastname: Critchley
authors.affiliation: Gurdon Institute and Department of Physics, University of Cambridge, Cambridge CB2 1QN, UK.|Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Simons
authors.affiliation: Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.|Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Myriam
authors.identifier: http://orcid.org/0000-0003-3332-6958
authors.initials: M
authors.lastname: Hemberger
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.|Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Bon-Kyoung
authors.initials: BK
authors.lastname: Koo
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.|Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Moffett
authors.affiliation: Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Graham J
authors.identifier: http://orcid.org/0000-0001-8677-4143
authors.initials: GJ
authors.lastname: Burton
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects* / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism*; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006801:Humans; D009940:Organoids / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D004967:Estrogens; D011374:Progesterone