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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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: | Date Event 21 January 2020 Published 2 January 2020 Accepted |
| 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 open licence) |
| Date of first compliant deposit: | 22 January 2020 |
| Date of first compliant Open Access: | 22 January 2020 |
| URI: | https://wrap.warwick.ac.uk/132226/ |
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