Transcriptomic signature of luteinized cumulus cells of oocytes developing to live birth after women received intracytoplasmic sperm injection

Abstract

ObjectiveTo compare the transcriptome of human cumulus cells (CCs) from oocytes with different outcomes (pregnancy yes/no, live birth yes/no), to identify noninvasive biomarkers for oocyte selection as well as new therapeutic targets to increase live birth rates from assisted reproductive technologies (ART). DesignRetrospective observational study. SubjectsSubfertile couples undergoing controlled ovarian superstimulation and intracytoplasmic sperm injection (ICSI) with subsequent unbiopsied embryo transfer (ET) below the female age of 43 years. Intervention(s)RNA sequencing (RNA-seq) of CCs from oocytes resulting in a pregnancy, no pregnancy, live birth and no live birth. Main outcome MeasuresDifferential gene expression (DEG) between CCs of oocytes resulting in A) “no pregnancy” versus “pregnancy” and B) “pregnancy only” versus “live birth”. ResultsWhile RNAseq did not reveal DEGs when comparing the transcriptomic profiles of the groups “no pregnancy” with “ pregnancy”, we identified 139 DEGs by comparing “pregnancy only” with “live birth” of which 28 belonged to clusters relevant to successful ART outcomes (i.e. CTGF, SERPINE2, PCK1, HHIP, HS3ST, BIRC5). A functional enrichment analysis revealed that the transcriptome of CCs associated with live birth depicts pathways of extracellular matrix, inflammatory cascades leading to ovulation, cell patterning, proliferation and differentiation, and silencing pathways leading to apoptosis. ConclusionWe identified a CCs transcriptomic profile associated with live birth after ET that, after further validation, could serve to predict successful ART outcomes. The definition of relevant pathways of CCs related to oocyte competency contributes to a broader understanding of the cumulus oocyte complex to identify further therapeutic targets for improving ART success.