Uterine selection of human embryos at implantation

Jan J. Brosens, Madhuri S. Salker, Gijs Teklenburg, Jaya Nautiyal, Scarlett Salter, Emma S. Lucas, Jennifer H. Steel, Mark Christian, Yi Wah Chan, Carolien M. Boomsma, Jonathan D. Moore, Geraldine M. Hartshorne, Sandra Šućurović, Biserka Mulac-Jericevic, Cobi J. Heijnen, Siobhan Quenby, Marian J. Groot Koerkamp, Frank C.P. Holstege, Anatoly Shmygol, Nick S. Macklon

Research output: Contribution to journalArticlepeer-review

180 Citations (Scopus)

Abstract

Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embryos elicit an endoplasmic stress response in human decidual cells. A stress response was also evident upon in vivo exposure of mouse uteri to culture medium conditioned by low-quality human embryos. By contrast, signals emanating from developmentally competent embryos activated a focused gene network enriched in metabolic enzymes and implantation factors. We further show that trypsin, a serine protease released by pre-implantation embryos, elicits Ca 2+ signaling in endometrial epithelial cells. Competent human embryos triggered short-lived oscillatory Ca 2+ fluxes whereas low-quality embryos caused a heightened and prolonged Ca 2+ response. Thus, distinct positive and negative mechanisms contribute to active selection of human embryos at implantation.

Original languageEnglish
Article number3894
JournalScientific reports
Volume4
DOIs
Publication statusPublished - Feb 6 2014
Externally publishedYes

ASJC Scopus subject areas

  • General

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