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Lucas, Emma S. et al (2020) Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Comm. Biology. 3 37 10.1038/s42003-020-0763-1

Lucas, Emma S. et al (2020) Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Comm. Biology. 3 37 10.1038/s42003-020-0763-1

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.

Thu 20 Feb 2020, 08:16