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

• DOI: 10.7554/elife.31274
• Publication Date: 2017-12-11T16:00:08Z
• Authors: Paul J Brighton; Yojiro Maruyama; Katherine Fishwick; Pavle Vrljicak; Shreeya Tewary; Risa Fujihara; Joanne Muter; Emma S Lucas; Taihei Yamada; Laura Woods; Raffaella Lucciola; Yie Hou Lee; Satoru Takeda; Sascha Ott; Myriam Hemberger; Siobhan Quenby; Jan Joris Brosens
• Keywords: Decidualization; Decidual cells; Senescence; Decidua

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 differentiation into decidual that control embryo implantation. Here we show FOXO1 also causes acute senescence of a subpopulation decidualizing EnSCs an IL-8 dependent manner. Selective depletion or enrichment this revealed drives transient inflammatory response associated with receptivity. Further, senescent prevent mesenchymal stem cultures. As progresses, IL-15 activated uterine natural killer (uNK) selectively target clear through granule exocytosis. Our findings reveal governs rejuvenation remodeling at implantation, suggest critical role for uNK maintaining homeostasis endometrium.