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Title:
Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window | Communications Biology
Description:
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.
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headline:Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window
description: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.
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name:University Hospitals Coventry & Warwickshire
address:
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
type:PostalAddress
type:Organization
name:University of Warwick
address:
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
type:PostalAddress
type:Organization
name:Sascha Ott
affiliation:
name:University Hospitals Coventry & Warwickshire
address:
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
type:PostalAddress
type:Organization
name:University of Warwick
address:
name:Department of Computer Science, University of Warwick, Coventry, UK
type:PostalAddress
type:Organization
name:Jan J. Brosens
url:http://orcid.org/0000-0003-0116-9329
affiliation:
name:University Hospitals Coventry & Warwickshire
address:
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
type:PostalAddress
type:Organization
name:University of Warwick
address:
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:School of Life Sciences, Gibbet Hill Campus, University of Warwick, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
name:Department of Computer Science, University of Warwick, Coventry, UK
name:Tommyâs National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, UK
name:Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK
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