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- Title
Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window.
- Authors
Lucas, Emma S.; Vrljicak, Pavle; Muter, Joanne; Diniz-da-Costa, Maria M.; Brighton, Paul J.; Kong, Chow-Seng; Lipecki, Julia; Fishwick, Katherine J.; Odendaal, Joshua; Ewington, Lauren J.; Quenby, Siobhan; Ott, Sascha; Brosens, Jan J.
- 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. Lucas, Vrljicak et al characterise how the cycling endometrium transitions to a pregnant state. Through single-cell analysis of endometrial stromal cells and timed endometrial biopsies they identify DIO2 and SCARA5 as markers of a divergent decidual response.
- Subjects
RECURRENT miscarriage; STROMAL cells; ENDOMETRIUM; EXTRACELLULAR matrix; ACUTE stress disorder
- Publication
Communications Biology, 2020, Vol 3, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-020-0763-1