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Sci Rep. 2014 Feb 6;4:3894. doi: 10.1038/srep03894.

Uterine selection of human embryos at implantation.

Author information

1
Division of Reproductive Health, Warwick Medical School, Clinical Sciences Research Laboratories, University Hospital, Coventry CV2 2DX, UK.
2
1] Division of Reproductive Health, Warwick Medical School, Clinical Sciences Research Laboratories, University Hospital, Coventry CV2 2DX, UK [2] Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London W12 ONN, UK.
3
Department for Reproductive Medicine and Gynecology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
4
Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London W12 ONN, UK.
5
Warwick Systems Biology Centre, University of Warwick, Coventry CV4 7AL, UK.
6
Department of Physiology and Immunology, Medical School, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
7
Molecular Cancer Research, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
8
1] Department for Reproductive Medicine and Gynecology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands [2] Division of Developmental Origins of Adult Diseases (DOHaD), University of Southampton, Coxford Road, Southampton SO16 5YA, UK.

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.

PMID:
24503642
PMCID:
PMC3915549
DOI:
10.1038/srep03894
[Indexed for MEDLINE]
Free PMC Article

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