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Clearance of senescent decidual cells by uterine natural killer cells drives endometrial remodeling during the window of implantation

Authors :
Katherine J. Fishwick
Yie Hou Lee
Pavle Vrljicak
Yojiro Maruyama
Myriam Hemberger
Taihei Yamada
Sascha Ott
Jan J. Brosens
Satoru Takeda
Raffaella Lucciola
Paul J. Brighton
Siobhan Quenby
Shreeya Tewary
Joanne Muter
Risa Fujihara
Emma S. Lucas
Laura Woods
Publication Year :
2017
Publisher :
Cold Spring Harbor Laboratory, 2017.

Abstract

SummaryIn 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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....7612751db51651725c5856a65b59710e