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

ABSTRACT

OBJECTIVE: To compare the transcriptome of human cumulus cells (CCs) from oocytes with different outcomes (pregnancy yes/no, live birth [LB] yes/no), to identify noninvasive biomarkers for oocyte selection as well as new therapeutic targets to increase LB rates from assisted reproductive technologies (ART). DESIGN: Retrospective observational study. SETTINGS This study was conducted at a University Hospital in Switzerland. PATIENTS Subfertile couples undergoing controlled ovarian superstimulation and intracytoplasmic sperm injection with subsequent unbiopsied embryo transfer below the female age of 43 years. INTERVENTION(S) RNA sequencing of CCs from oocytes results in a pregnancy, no pregnancy, LB, or no LB. MAIN OUTCOME MEASURES: Differential gene expression (DEG) between CCs of oocytes results in "no pregnancy" vs. "pregnancy" and "pregnancy only" vs. "live birth." RESULTS: Although RNA sequencing 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, and BIRC5). A functional enrichment analysis revealed that the transcriptome of CCs associated with LB depicts pathways of extracellular matrix, inflammatory cascades leading to ovulation, cell patterning, proliferation, and differentiation, and silencing pathways leading to apoptosis. CONCLUSION: We identified a CCs transcriptomic profile associated with LB after embryo transfer 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 and helps identify further therapeutic targets for improving ART success.