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Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window

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Lucas, Emma S., Vrljicak, Pavle, Muter, Joanne, Diniz-da-Costa, Maria, Brighton, Paul (Paul J.), Kong, Chow-Seng, Lipecki, Julia, Fishwick, Katherine J., Odendaal, Joshua, Ewington, Lauren J., Quenby, Siobhan, Ott, Sascha and Brosens, Jan J. (2020) Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Communications Biology, 3 (1). 37. doi:10.1038/s42003-020-0763-1 ISSN 2399-3642.

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Official URL: http://dx.doi.org/10.1038/s42003-020-0763-1

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Abstract

During the implantation window, the endometrium becomes poised to transition to a pregnant state, a process driven by differentiation of stromal cells into decidual cells (DC). Perturbations in this process, termed decidualization, leads to breakdown of the feto-maternal interface and miscarriage, but the underlying mechanisms are poorly understood. Here, we reconstructed the decidual pathway at single-cell level in vitro and demonstrate that stromal cells first mount an acute stress response before emerging as DC or senescent DC (snDC). In the absence of immune cell-mediated clearance of snDC, secondary senescence transforms DC into progesterone-resistant cells that abundantly express extracellular matrix remodelling factors. Additional single-cell analysis of midluteal endometrium identified DIO2 and SCARA5 as marker genes of a diverging decidual response in vivo. Finally, we report a conspicuous link between a pro-senescent decidual response in peri-implantation endometrium and recurrent pregnancy loss, suggesting that pre-pregnancy screening and intervention may reduce the burden of miscarriage.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: Communications Biology
Publisher: Nature Publishing Group
ISSN: 2399-3642
Official Date: 21 January 2020
Dates:
DateEvent
21 January 2020Published
2 January 2020Accepted
Volume: 3
Number: 1
Article Number: 37
DOI: 10.1038/s42003-020-0763-1
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 22 January 2020
Date of first compliant Open Access: 22 January 2020

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