title: Characterization and quantification of proteins secreted by single human embryos prior to implantation.
abstract: The use of in vitro fertilization (IVF) has revolutionized the treatment of infertility and is now responsible for 1-5% of all births in industrialized countries. During IVF, it is typical for patients to generate multiple embryos. However, only a small proportion of them possess the genetic and metabolic requirements needed in order to produce a healthy pregnancy. The identification of the embryo with the greatest developmental capacity represents a major challenge for fertility clinics. Current methods for the assessment of embryo competence are proven inefficient, and the inadvertent transfer of non-viable embryos is the principal reason why most IVF treatments (approximately two-thirds) end in failure. In this study, we investigate how the application of proteomic measurements could improve success rates in clinical embryology. We describe a procedure that allows the identification and quantification of proteins of embryonic origin, present in attomole concentrations in the blastocoel, the enclosed fluid-filled cavity that forms within 5-day-old human embryos. By using targeted proteomics, we demonstrate the feasibility of quantifying multiple proteins in samples derived from single blastocoels and that such measurements correlate with aspects of embryo viability, such as chromosomal (ploidy) status. This study illustrates the potential of high-sensitivity proteomics to measure clinically relevant biomarkers in minute samples and, more specifically, suggests that key aspects of embryo competence could be measured using a proteomic-based strategy, with negligible risk of harm to the living embryo. Our work paves the way for the development of "next-generation" embryo competence assessment strategies, based on functional proteomics.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, Institute of Reproductive Sciences University of Oxford, Oxford, UK Oxford Fertility Unit, Institute of Reproductive Sciences, Oxford, UK Reprogenetics UK, Institute of Reproductive Sciences, Oxford, UK.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Poli
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ori
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, Institute of Reproductive Sciences University of Oxford, Oxford, UK Oxford Fertility Unit, Institute of Reproductive Sciences, Oxford, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Child
authors.affiliation: Reprogenetics UK, Institute of Reproductive Sciences, Oxford, UK.
authors.forename: Souraya
authors.initials: S
authors.lastname: Jaroudi
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, Institute of Reproductive Sciences University of Oxford, Oxford, UK Reprogenetics UK, Institute of Reproductive Sciences, Oxford, UK.
authors.forename: Katharina
authors.initials: K
authors.lastname: Spath
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Beck
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, Institute of Reproductive Sciences University of Oxford, Oxford, UK Reprogenetics UK, Institute of Reproductive Sciences, Oxford, UK dagan.wells@obs-gyn.ox.ac.uk.
authors.forename: Dagan
authors.initials: D
authors.lastname: Wells
mesh_terms: D000328:Adult; D001755:Blastocyst / Q000737:chemistry*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods; D006801:Humans; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D016019:Survival Analysis
chemical_list: D011506:Proteins; D020543:Proteome
keywords: blastocoel; gene expression; human embryo; in vitro fertilization; proteomics