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Cited by 269

The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.

Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids

Open access
Rawlings, Thomas M, Makwana, Komal, Taylor, Deborah M, Molè, Matteo A, Fishwick, Katherine J, Tryfonos, Maria, Odendaal, Joshua, Hawkes, Amelia, Zernicka-Goetz, Magdalena, Hartshorne, Geraldine M, Brosens, Jan J, Lucas, Emma S·2021·eLife

Abstract

Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into a robust matrix that accommodates the placenta throughout pregnancy. To gain insights into the underlying mechanisms, we established and characterized endometrial assembloids, consisting of gland-like organoids and primary stromal cells. Single-cell transcriptomics revealed that decidualized assembloids closely resemble midluteal endometrium, harbouring differentiated and senescent subpopulations in both glands and stroma. We show that acute senescence in glandular epithelium drives secretion of multiple canonical implantation factors, whereas in the stroma it calibrates the emergence of anti-inflammatory decidual cells and pro-inflammatory senescent decidual cells. Pharmacological inhibition of stress responses in pre-decidual cells accelerated decidualization by eliminating the emergence of senescent decidual cells. In co-culture experiments, accelerated decidualization resulted in entrapment of collapsed human blastocysts in a robust, static decidual matrix. By contrast, the presence of senescent decidual cells created a dynamic implantation environment, enabling embryo expansion and attachment, although their persistence led to gradual disintegration of assembloids. Our findings suggest that decidual senescence controls endometrial fate decisions at implantation and highlight how endometrial assembloids may accelerate the discovery of new treatments to prevent reproductive failure.

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Metadata

Authors
Rawlings, T. M., Makwana, K., Taylor, D. M., Molè, M. A., Fishwick, K. J., Tryfonos, M., Odendaal, J., Hawkes, A., Zernicka-Goetz, M., Hartshorne, G. M., Brosens, J. J., & Lucas, E. S.
Venue
eLife
Published
2021-09-06
Volume
10
ISSN
2050-084X (ISSN-L)
OpenAlex
W3198684516
Cited by
269
References
84
FWCI
11.97
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids. https://app.cochat.ai/papers/10.7554/elife.69603
The paper
Rawlings, T. M., Makwana, K., Taylor, D. M., Molè, M. A., Fishwick, K. J., Tryfonos, M., Odendaal, J., Hawkes, A., Zernicka-Goetz, M., Hartshorne, G. M., Brosens, J. J., & Lucas, E. S. (2021). Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids. eLife. https://doi.org/10.7554/elife.69603

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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