The Library
Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids
Tools
Tools
Tools
Rawlings, Thomas M., Makwana, Komal, Taylor, Deborah, Molè, Matteo A., Fishwick, Katherine J., Tryfonos, Maria, Odendaal, Joshua, Hawkes, Amelia, Zernicka-Goetz, Magdalena, Hartshorne, Geraldine M., Brosens, Jan J. and Lucas, Emma S. (2021) Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids. eLife, 10 . e69603. doi:10.7554/elife.69603 ISSN 2050-084X.
|
PDF
WRAP-Modelling-impact-decidual-senescence-embryo-implantation-human-endometrial-assembloids-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (115Mb) | Preview |
Official URL: https://doi.org/10.7554/elife.69603
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.
| Item Type: | Journal Article | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > RG Gynecology and obstetrics |
|||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||||||||
| SWORD Depositor: | Library Publications Router | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | Cells -- Aging, Endometrium, Human embryo -- Transplantation -- Mathematical models, Infertility, Female -- Treatment, Miscarriage | |||||||||||||||
| Journal or Publication Title: | eLife | |||||||||||||||
| Publisher: | eLife Sciences Publications, Ltd | |||||||||||||||
| ISSN: | 2050-084X | |||||||||||||||
| Official Date: | 18 October 2021 | |||||||||||||||
| Dates: |
|
|||||||||||||||
| Volume: | 10 | |||||||||||||||
| Article Number: | e69603 | |||||||||||||||
| DOI: | 10.7554/elife.69603 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
| Copyright Holders: | © 2021, Rawlings et al. | |||||||||||||||
| Date of first compliant deposit: | 28 October 2021 | |||||||||||||||
| Date of first compliant Open Access: | 28 October 2021 | |||||||||||||||
| RIOXX Funder/Project Grant: |
|
|||||||||||||||
| Related URLs: | ||||||||||||||||
| Contributors: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
