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

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


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.

MeSH terms

  • Adult Stem Cells / drug effects*
  • Adult Stem Cells / metabolism
  • Cell Culture Techniques*
  • Cell Differentiation / drug effects
  • Cell Lineage
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Culture Media / chemistry
  • Culture Media / metabolism*
  • Decidua / cytology
  • Decidua / drug effects
  • Decidua / metabolism
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Endometrium / cytology
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Estrogens / pharmacology*
  • Female
  • Gene Expression Regulation, Developmental
  • Genotype
  • Humans
  • Organoids / cytology
  • Organoids / drug effects*
  • Organoids / metabolism
  • Phenotype
  • Pregnancy
  • Progesterone / pharmacology*
  • Time Factors
  • Tissue Engineering / methods*
  • Tumor Cells, Cultured


  • Culture Media
  • Estrogens
  • Progesterone