Uterine selection of human embryos at implantation.
Sci Rep, 2014/2/06;4:3894.
Brosens JJ[1], Salker MS[2], Teklenburg G[3], Nautiyal J[4], Salter S[1], Lucas ES[1], Steel JH[4], Christian M[1], Chan YW[5], Boomsma CM[3], Moore JD[5], Hartshorne GM[1], Sućurović S[6], Mulac-Jericevic B[6], Heijnen CJ[3], Quenby S[1], Koerkamp MJ[7], Holstege FC[7], Shmygol A[1], Macklon NS[8]
Affiliations
PMID: 24503642DOI: 10.1038/srep03894
Impact factor: 4.996
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.
MeSH terms
Animals; Blastocyst; Calcium Signaling; Cells, Cultured; Chromosome Aberrations; Culture Media, Conditioned; Decidua; Embryo Implantation; Embryo, Mammalian; Endoplasmic Reticulum Stress; Epithelial Cells; Female; Gene Expression Profiling; HSC70 Heat-Shock Proteins; Humans; Insulin-Like Growth Factor Binding Protein 1; Mice; Mice, Inbred C57BL; Prolactin; RNA Interference; RNA, Small Interfering; Signal Transduction; Trypsin; Uterus
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