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Cited by 459Reproductive Biology and FertilityReproductive System and PregnancyPluripotent Stem Cells Research

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

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Boretto, Matteo, Cox, Benoit, Noben, Manuel, Hendriks, Nikolai, Fassbender, Amelie, Roose, Heleen, Amant, Frédéric, Timmerman, Dirk +5 more·2017·Development
DOI 10.1242/dev.148478
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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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Authors
Boretto, M., Cox, B., Noben, M., Hendriks, N., Fassbender, A., Roose, H., Amant, F., Timmerman, D., Tomassetti, C., Vanhie, A., Meuleman, C., Ferrante, M., & Vankelecom, H.
Affiliations
  • KU Leuven (BE)
  • Universitair Ziekenhuis Leuven (BE)
Corresponding author
Vankelecom, Hugo
ORCID
Venue
Development
Publisher
The Company of Biologists
Published
2017-05-15
Volume
144
Issue
10
Pages
1775-1786
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.148478
OpenAlex
W2607762218
Cited by
459
References
68
Citations by year
2026: 83 · 2025: 69 · 2024: 45 · 2023: 58 · 2022: 60 · 2021: 53 · 2020: 43 · 2019: 29 · 2018: 14 · 2017: 4 · 2016: 1
FWCI
23.63
Type
journal article
Language
en
Open access
Licence
www.biologists.com/user-licence-1-1/ (vor, 184 d)
Locations
  • Development (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Lirias (submittedVersion, other-oa)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • KU Leuven
  • Fonds Wetenschappelijk Onderzoek
  • Agentschap voor Innovatie door Wetenschap en Technologie
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
endometrial organoids, endometrium, endometrial epithelium, Wnt signaling, Matrigel, organoid expansion, menstrual cycle, estrogen, progesterone, cell proliferation, human endometrium, tissue remodeling
MeSH terms
R-Spondins, Animals, Cell Differentiation, Cells, Cultured, Endometrium, Epithelial Cells, Epithelium, Female, Humans, Organoids, Phenotype, Cell Culture Techniques, Thrombospondins, Cell Proliferation, Mice, Wnt3A Protein

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