The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and human endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT-activating conditions, swiftly formed organoid structures that showed long-term expansion capacity, and reproduced the molecular and histological phenotype of the tissue's epithelium. The supplemented WNT level determined the type of mouse endometrial organoids obtained: high WNT yielded cystic organoids displaying a more differentiated phenotype than the dense organoids obtained in low WNT. The organoids phenocopied physiological responses of endometrial epithelium to hormones, including increased cell proliferation under estrogen and maturation upon progesterone. Moreover, the human endometrial organoids replicated the menstrual cycle under hormonal treatment at both the morpho-histological and molecular levels. Together, we established an organoid culture system for endometrium, reproducing tissue epithelium physiology and allowing long-term expansion. This novel model provides a powerful tool for studying mechanisms underlying the biology as well as the pathology of this key reproductive organ.
The authors declare no competing or financial interests.
Conceptualization: M.B., B.C., A.F., A.V., C.M., H.V.; Methodology: M.B., B.C., M.N., N.H., H.R., M.F., H.V.; Software: M.B., H.V.; Validation: M.B., H.V.; Formal analysis: M.B., B.C., H.V.; Investigation: M.B., B.C., M.N., N.H., H.R., H.V.; Resources: M.B., M.N., N.H., A.F., F.A., D.T., C.T., A.V., C.M., M.F., H.V.; Data curation: M.B., B.C., H.V.; Writing - original draft: M.B., B.C., M.N., H.V.; Writing - review & editing: M.B., B.C., H.V.; Visualization: M.B., H.V.; Supervision: H.V.; Project administration: H.V.; Funding acquisition: H.V.
This work was supported by grants from the KU Leuven (Research Fund; GOA) and from the Fonds Wetenschappelijk Onderzoek (FWO). M.B. is a PhD Fellow supported by the GOA grant. B.C. and M.N. are supported by a PhD Fellowship from the Fonds Wetenschappelijk Onderzoek, and H.R. is supported by a PhD Fellowship from the Agentschap voor Innovatie door Wetenschap en Technologie (IWT). D.T. and M.F. are Senior Clinical Investigators of the Fonds Wetenschappelijk Onderzoek.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.148478.supplemental
- Received December 20, 2016.
- Accepted April 3, 2017.