Endometrial Organoid Models and Cellular Dynamics

The endometrium is a highly dynamic mucosal tissue that undergoes cyclical remodelling under hormonal regulation, preparing for embryo implantation and sustaining early pregnancy. Traditional two‐dimensional cultures and animal models have provided valuable insights but lack the cellular complexity and spatial architecture of native human tissue. Endometrial organoid systems and assembloids overcome these limitations by recreating three‐dimensional glandular and stromal compartments, enabling the study of epithelial–stromal crosstalk, hormonal responsiveness and the emergence of specialised lineages such as secretory and ciliated cells. Advances in extracellular matrix design, microfluidic co‐culture and air–liquid interface methods have refined these models to include intact luminal epithelium, dynamic decidualisation and physiologically relevant mechanical cues. Single‐cell transcriptomics and spatial mapping further illuminate cell fate decisions and signalling pathways—such as WNT and NOTCH—that govern epithelial differentiation, stromal transformation and the window of receptivity. Together, these organoid platforms offer unprecedented opportunities to investigate implantation biology, endometrial disorders and personalised therapeutic strategies.

Research from Nature Portfolio

Recent studies have produced dense single‐cell and spatial reference maps of both human uterine tissue and three‐dimensional endometrial organoids. By dissecting signalling cascades that direct secretory and ciliated lineage specification in glandular and luminal niches, researchers have shown how modulation of WNT or NOTCH pathways enhances differentiation efficiency. These cellular atlases have also been applied to deconvolute bulk transcriptomes from endometrial cancers and endometriotic lesions, illuminating the dominant cell types in each disorder and offering mechanistic insights for future therapeutic development. In addition, non‐invasive derivation of organoids from menstrual flow has been demonstrated to yield cultures with transcriptomic fidelity to biopsy‐derived counterparts. Such organoids respond comparably to oestrogen, progesterone and early pregnancy hormones, reproducing morphological changes and ‘uterine milk’ protein secretion, and hold promise for personalised investigation of gynaecological conditions and assisted‐reproduction failure.

Endometrial Organoid Models and Cellular Dynamics publication trend

The graph below shows the total number of articles in endometrial organoid models and cellular dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Organoid: Three‐dimensional multicellular in vitro model replicating the architecture and function of native tissue.

Assembloid: Organ‐like structure co‐cultured with multiple cell types to mimic tissue heterogeneity and intercellular communication.

Decidualisation: Hormone‐driven differentiation of endometrial stromal cells preparing the uterine lining for embryo implantation.

Luminal epithelium: Innermost epithelial layer of the endometrium that interfaces directly with the implanting embryo.

Extracellular matrix (ECM): Network of proteins and polysaccharides providing structural support and biochemical cues to cells.

References

1. Generation of Human Endometrial Assembloids with a Luminal Epithelium using Air–Liquid Interface Culture Methods. Advanced Science (2023).
2. Photo-Cross-linked Gelatin Methacryloyl Hydrogels Enable the Growth of Primary Human Endometrial Stromal Cells and Epithelial Gland Organoids. ACS Applied Materials & Interfaces (2024).
3. Menstrual flow as a non-invasive source of endometrial organoids. Communications Biology (2021).
4. Three-dimensional culture models of human endometrium for studying trophoblast-endometrium interaction during implantation. Reproductive Biology and Endocrinology (2022).
5. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro. Nature Genetics (2021).