PT  - JOURNAL ARTICLE
AU  - Paul J Brighton
AU  - Yojiro Maruyama
AU  - Katherine Fishwick
AU  - Pavle Vrljicak
AU  - Shreeya Tewary
AU  - Risa Fujihara
AU  - Joanne Muter
AU  - Emma S Lucas
AU  - Taihei Yamada
AU  - Laura Woods
AU  - Raffaella Lucciola
AU  - Yie Hou Lee
AU  - Satoru Takeda
AU  - Sascha Ott
AU  - Myriam Hemberger
AU  - Siobhan Quenby
AU  - Jan J Brosens
TI  - Clearance of senescent decidual cells by uterine natural killer cells drives endometrial remodeling during the window of implantation
AID  - 10.1101/172593
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 172593
4099  - http://biorxiv.org/content/early/2017/08/04/172593.short
4100  - http://biorxiv.org/content/early/2017/08/04/172593.full
AB  - 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.