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

MY Turco, L Gardner, J Hughes, T Cindrova-Davies… - Nature cell …, 2017 - nature.com
MY Turco, L Gardner, J Hughes, T Cindrova-Davies, MJ Gomez, L Farrell, M Hollinshead…
Nature cell biology, 2017nature.com
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 …
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.
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