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dc.contributor.authorRawlings, Thomas M
dc.contributor.authorMakwana, Komal
dc.contributor.authorTaylor, Deborah M
dc.contributor.authorMolè, Matteo A
dc.contributor.authorFishwick, Katherine J
dc.contributor.authorTryfonos, Maria
dc.contributor.authorOdendaal, Joshua
dc.contributor.authorHawkes, Amelia
dc.contributor.authorZernicka-Goetz, Magdalena
dc.contributor.authorHartshorne, Geraldine M
dc.contributor.authorBrosens, Jan J
dc.contributor.authorLucas, Emma S
dc.date.accessioned2021-11-25T17:29:16Z
dc.date.available2021-11-25T17:29:16Z
dc.date.issued2021-09-06
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331190
dc.description.abstractDecidual 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.
dc.format.mediumElectronic
dc.languageeng
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleModelling the impact of decidual senescence on embryo implantation in human endometrial assembloids.
dc.typeArticle
prism.publicationDate2021
prism.publicationNameElife
prism.volume10
dc.identifier.doi10.17863/CAM.78637
dc.identifier.doi10.17863/CAM.78637
dcterms.dateAccepted2021-09-03
rioxxterms.versionofrecord10.7554/eLife.69603
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-09-06
dc.contributor.orcidZernicka-Goetz, Magdalena [0000-0002-7004-2471]
dc.contributor.orcidBrosens, Jan J [0000-0003-0116-9329]
dc.contributor.orcidLucas, Emma S [0000-0002-8571-8921]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-09-06


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International