In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-12-11)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2050-084X
DOI:
10.7554/eLife.31274.001
DOI:
10.7554/eLife.31274.002
DOI:
10.7554/eLife.31274.004
DOI:
10.7554/eLife.31274.003
DOI:
10.7554/eLife.31274.005
DOI:
10.7554/eLife.31274.006
DOI:
10.7554/eLife.31274.007
DOI:
10.7554/eLife.31274.009
DOI:
10.7554/eLife.31274.008
DOI:
10.7554/eLife.31274.010
DOI:
10.7554/eLife.31274.012
DOI:
10.7554/eLife.31274.011
DOI:
10.7554/eLife.31274.013
DOI:
10.7554/eLife.31274.015
DOI:
10.7554/eLife.31274.014
DOI:
10.7554/eLife.31274.016
DOI:
10.7554/eLife.31274.017
DOI:
10.7554/eLife.31274.018
DOI:
10.7554/eLife.31274.019
DOI:
10.7554/eLife.31274.020
DOI:
10.7554/eLife.31274.021
Sprache:
Englisch
Verlag:
eLife Sciences Publications, Ltd
Publikationsdatum:
2017
ZDB Id:
2687154-3
