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Uterine Selection of Human Embryos at Implantation

2014; Nature Portfolio; Volume: 4; Issue: 1 Linguagem: Inglês

10.1038/srep03894

2045-2322

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 Hartshorne, Sandra Šućurović, Biserka Mulac‐Jeričević, Cobi J. Heijnen, Siobhan Quenby, Marian J.A. Groot Koerkamp, Frank C. P. Holstege, Anatoly Shmygol, Nick Macklon,

Reproductive Physiology in Livestock

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 Ca2+ signaling in endometrial epithelial cells. Competent human embryos triggered short-lived oscillatory Ca2+ fluxes whereas low-quality embryos caused a heightened and prolonged Ca2+ response. Thus, distinct positive and negative mechanisms contribute to active selection of human embryos at implantation.