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Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium

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Brighton, Paul (Paul J.), Maruyama, Yojiro, Fishwick, Katherine, Vrljicak, Pavle, Tewary, Shreeya, Fujihara, Risa, Muter, Joanne, Lucas, Emma S., Yamada, Taihei, Woods, Laura, Lucciola, Raffaella, Lee, Yie Hou, Takeda, Satoru, Ott, Sascha, Hemberger, Myriam, Quenby, Siobhan and Brosens, Jan J. (2017) Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. eLife, 6 . e31274. doi:10.7554/eLife.31274

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Official URL: https://doi.org/10.7554/eLife.31274

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Abstract

In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells that control embryo implantation. Here we show that FOXO1 also causes acute senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner. Selective depletion or enrichment of this subpopulation revealed that decidual senescence drives the transient inflammatory response associated with endometrial receptivity. Further, senescent cells prevent differentiation of endometrial mesenchymal stem cells in decidualizing cultures. As the cycle progresses, IL-15 activated uterine natural killer (uNK) cells selectively target and clear senescent decidual cells through granule exocytosis. Our findings reveal that acute decidual senescence governs endometrial rejuvenation and remodeling at embryo implantation, and suggest a critical role for uNK cells in maintaining homeostasis in cycling endometrium.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Endometrium, Endometrium -- Diseases, Fertility, Human, Ovum implantation, Fertilization in vitro, Human, Killer cells
Journal or Publication Title: eLife
Publisher: eLife Sciences Publications Ltd.
ISSN: 2050-084X
Book Title: Clearance of senescent decidual cells by uterine natural killer cells drives endometrial remodeling during the window of implantation
Official Date: 11 December 2017
Dates:
DateEvent
11 December 2017Available
2 December 2017Accepted
Date of first compliant deposit: 6 December 2017
Volume: 6
Article Number: e31274
DOI: 10.7554/eLife.31274
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
RMRRH0035Tommy's National Miscarriage Research CentreUNSPECIFIED
RMRRH0019University Hospitals Coventry and WarwickshireUNSPECIFIED
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