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Nat Cell Biol. 2017 May;19(5):568-577. doi: 10.1038/ncb3516. Epub 2017 Apr 10.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

Author information

1
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
2
Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
3
Department of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2SP, UK.
4
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
5
Anthony Nolan Research Institute, Royal Free Hospital, London, NW3 2QU, UK.
6
Division of Reproductive Health, Clinical Science Research Laboratories, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
7
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK.
8
Gurdon Institute and Department of Physics, University of Cambridge, Cambridge CB2 1QN, UK.
9
Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.
10
Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
11
Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.

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.

PMID:
28394884
PMCID:
PMC5410172
DOI:
10.1038/ncb3516
[Indexed for MEDLINE]
Free PMC Article

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