Proteomic analysis of individual human embryos to identify novel biomarkers of development and viability

Objective: To develop a method to analyze the proteome of individual human blastocysts and identify differentially expressed proteins prior to implantation. Design: Experimental study. Setting: Research environment. Patient(s): Couples undergoing infertility treatment donated with consent cryopreserved human cleavage-stage embryos for research. Intervention(s): Individual embryos were extracted and analyzed by time-of-flight mass spectrometry. Main Outcome Measure(s): The protein expression profiles of individual embryos. Result(s): Differential protein expression profiles were observed between early and expanded blastocysts, as well as between developing blastocysts and degenerate embryos. Significantly, several up-regulated and down-regulated proteins were detected in degenerating embryos. A search in the protein databases highlighted several candidates, including an inhibitor of Tcf-4 (transcription factor mediating Wnt signaling) and an apoptotic protease-activating factor. Conclusion(s): This is the first study to successfully analyze the proteome of individual human embryos. This study has shown that protein expression profiles relate to morphology, with degenerating embryos exhibiting significant up-regulation of several potential biomarkers that might be involved in apoptotic and growth-inhibiting pathways.