eLife (Dec 2017)

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

  • 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

DOI
https://doi.org/10.7554/eLife.31274
Journal volume & issue
Vol. 6

Abstract

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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.

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