Altered cumulus cell transcripts in association with non-viable outcome

Abstract

OBJECTIVE: Cumulus cell (CC) gene expression analysis has been investigated as a non-invasive approach to assess an oocyte's ability to undergo normal fertilization, embryogenesis and establish a viable pregnancy. This study investigated the ability of CC gene expression profiles to reflect embryo implantation and non-viable outcome.DESIGN: Experimental Study.MATERIALS AND METHODS: CCs from individual COCs were collected with IRB consent and oocytes were cultured individually until the blastocyst stage. Trophectoderm biopsy was performed for comprehensive chromosome screening to identify euploid blastocysts. Single oocyte derived CCs (n=9) were grouped according to outcome following euploid blastocyst transfer: implantation with fetal cardiac activity (n=5) or non-viable outcome (n=4), with total RNA isolated for transcriptome analysis using the Codelink microarray platform.RESULTS: A total of 614 CC transcripts were observed to be >2 fold differentially expressed between positive implantation and non-viable outcome following D5 transfer with euploid blastocysts. There were 147 CC transcripts increased (24%) and 467 CC transcripts decreased (76%) in expression with non-viable loss. Gene ontology annotation of these differentially expressed transcripts identified biological processes such as transport, response to external stimuli and cell surface receptor linked signal transduction. Annotation of cellular location revealed 39% of these genes as membrane bound and 13% extracellular. The bidirectional communication between the oocyte and CCs is crucial for oogenesis and is controlled through gap junctions and secreted paracrine factors. Validation of these differentially expressed transcripts is ongoing.CONCLUSION: This study contributes further data for the consideration of CC gene expression profiles to reflect the developmental competence of the maturing oocyte. Further studies to characterize these differentially expressed genes and their functions are essential to the continuing understanding of this relationship. OBJECTIVE: Cumulus cell (CC) gene expression analysis has been investigated as a non-invasive approach to assess an oocyte's ability to undergo normal fertilization, embryogenesis and establish a viable pregnancy. This study investigated the ability of CC gene expression profiles to reflect embryo implantation and non-viable outcome. DESIGN: Experimental Study. MATERIALS AND METHODS: CCs from individual COCs were collected with IRB consent and oocytes were cultured individually until the blastocyst stage. Trophectoderm biopsy was performed for comprehensive chromosome screening to identify euploid blastocysts. Single oocyte derived CCs (n=9) were grouped according to outcome following euploid blastocyst transfer: implantation with fetal cardiac activity (n=5) or non-viable outcome (n=4), with total RNA isolated for transcriptome analysis using the Codelink microarray platform. RESULTS: A total of 614 CC transcripts were observed to be >2 fold differentially expressed between positive implantation and non-viable outcome following D5 transfer with euploid blastocysts. There were 147 CC transcripts increased (24%) and 467 CC transcripts decreased (76%) in expression with non-viable loss. Gene ontology annotation of these differentially expressed transcripts identified biological processes such as transport, response to external stimuli and cell surface receptor linked signal transduction. Annotation of cellular location revealed 39% of these genes as membrane bound and 13% extracellular. The bidirectional communication between the oocyte and CCs is crucial for oogenesis and is controlled through gap junctions and secreted paracrine factors. Validation of these differentially expressed transcripts is ongoing. CONCLUSION: This study contributes further data for the consideration of CC gene expression profiles to reflect the developmental competence of the maturing oocyte. Further studies to characterize these differentially expressed genes and their functions are essential to the continuing understanding of this relationship.