title: Distinct differences in global gene expression profiles in non-implanted blastocysts and blastocysts resulting in live birth.
abstract: Results from animal models points towards the existence of a gene expression profile that is distinguishably different in viable embryos compared with non-viable embryos. Knowledge of human embryo transcripts is however limited, in particular with regard to how gene expression is related to clinical outcome. The purpose of the present study was therefore to determine the global gene expression profiles of human blastocysts. Next Generation Sequencing was used to identify genes that were differentially expressed in non-implanted embryos and embryos resulting in live birth. Three trophectoderm biopsies were obtained from morphologically high quality blastocysts resulting in live birth and three biopsies were obtained from non-implanting blastocysts of a comparable morphology. Total RNA was extracted from all samples followed by complete transcriptome sequencing. Using a set of filtering criteria, we obtained a list of 181 genes that were differentially expressed between trophectoderm biopsies from embryos resulting in either live birth or no implantation (negative hCG), respectively. We found that 37 of the 181 genes displayed significantly differential expression (p<0.05), e.g. EFNB1, CYTL1 and TEX26 and TESK1, MSL1 and EVI5 in trophectoderm biopsies associated with live birth and non-implanting, respectively. Out of the 181 genes, almost 80% (145 genes) were up-regulated in biopsies from un-implanted embryos, whereas only 20% (36 genes) showed an up-regulation in the samples from embryos resulting in live birth. Our findings suggest the presence of molecular differences visually undetectable between implanted and non-implanted embryos, and represent a proof of principle study.
authors.affiliation: Centre for Preimplantation Genetic Diagnosis, The Fertility Clinic, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200, Aarhus N, Denmark. Electronic address: Kirstine.kirkegaard@ki.au.dk.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Kirkegaard
authors.affiliation: Aarhus University, Bioinformatics Research Center (BIRC), C.F. Møllers Allé 8, DK-8000, Aarhus C, Denmark.
authors.forename: Palle
authors.initials: P
authors.lastname: Villesen
authors.affiliation: Aarhus University, Bioinformatics Research Center (BIRC), C.F. Møllers Allé 8, DK-8000, Aarhus C, Denmark.
authors.forename: Jacob Malte
authors.initials: JM
authors.lastname: Jensen
authors.affiliation: Centre for Preimplantation Genetic Diagnosis, The Fertility Clinic, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200, Aarhus N, Denmark.
authors.forename: Johnny Juhl
authors.initials: JJ
authors.lastname: Hindkjær
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, DK-7100 Vejle, Denmark; Institute of Regional Health Services Research, University of Southern Denmark, DK-5000 Odense, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Kølvraa
authors.affiliation: Centre for Preimplantation Genetic Diagnosis, The Fertility Clinic, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200, Aarhus N, Denmark; Aarhus University, Department of Clinical Medicine, Brendstrupgaardsvej 100, DK-8200, Aarhus N, Denmark.
authors.forename: Hans Jakob
authors.initials: HJ
authors.lastname: Ingerslev
authors.affiliation: Aarhus University, Department of Biomedicine, Wilhelm Meyers Allé 4, DK-8000, Aarhus C, Denmark; Aarhus Institute of Advanced Studies, Aarhus University, Høegh-Guldbergs Gade 6B, DK-8000, Aarhus C, Denmark. Electronic address: kly@biomed.au.dk.
authors.forename: Karin
authors.initials: K
authors.lastname: Lykke-Hartmann
mesh_terms: D000328:Adult; D001706:Biopsy; D001755:Blastocyst / Q000378:metabolism* / Q000473:pathology; D004475:Ectoderm / Q000378:metabolism / Q000473:pathology; D010064:Embryo Implantation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D050498:Live Birth / Q000235:genetics; D011247:Pregnancy; D056826:Single Embryo Transfer; D059467:Transcriptome
keywords: Blastocyst; Embryology; Gene expression; NGS; Pregnancy