Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability

Matteo Boretto, Benoit Cox, Manuel Noben, Nikolai Hendriks, Amelie Fassbender, Heleen Roose, Frédéric Amant, D. Timmerman, Dirk Timmerman, Carla Tomassetti, Arne Vanhie, Christel Meuleman, Marc Ferrante, Hugo Vankelecom
Development (Cambridge, England) · 2017 · vol. 144(10) , pp. 1775–1786 · doi:10.1242/dev.148478 · PMID:28442471 · W2607762218
Lab / animal OA: bronze CC0 ⤵ 64 in-corpus citations
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This study developed mouse and human endometrial organoids that replicate epithelium physiology, hormone responses, and the menstrual cycle, offering a new model for studying endometrial biology.

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Abstract

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.

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MeSH descriptors

Cell Culture Techniques Cell Proliferation Cell Proliferation Endometrium Endometrium Epithelium Organoids Animals Cell Culture Techniques Cell Differentiation Cell Differentiation Cells, Cultured Endometrium Epithelial Cells Epithelial Cells Epithelial Cells Epithelium Female Humans Mice

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