Abstract
Granulosa cells (GCs) play a critical role in driving the formation of ovarian follicles and building the cumulus-oocyte complex surrounding the ovum. We are particularly interested in assessing oocyte quality by examining the detailed gene expression profiles of human cumulus single cells. Using single-cell RNAseq techniques, we extensively investigated the single-cell transcriptomes of the cumulus GC populations from two women with normal ovarian function. This allowed us to elucidate the endogenous heterogeneity of GCs by uncovering the hidden GC subpopulation. The subsequent validation results suggest that CD24(+) GCs are essential for triggering ovulation. Treatment with human chorionic gonadotropin (hCG) significantly increases the expression of CD24 in GCs. CD24 in cultured human GCs is associated with hCG-induced upregulation of prostaglandin synthase (ARK1C1, PTGS2, PTGES, and PLA2G4A) and prostaglandin transporter (SLCO2A1 and ABCC4) expression, through supporting the EGFR-ERK1/2 pathway. In addition, it was observed that the fraction of CD24(+) cumulus GCs decreases in PCOS patients compared to that of controls. Altogether, the results support the finding that CD24 is an important mediator of ovulation and that it may also be used for therapeutic target of ovulatory disorders.
Highlights
In humans, ovarian folliculogenesis is a complex physiological process that underlies the health of the subsequent embryo and offspring[1,2]
Decreased mRNA abundances of CD24, PTGS2, SLCO2A1, PTGES, ARK1C1, PLA2G4A, and ABCC4 were observed in Granulosa cells (GCs) of polycystic ovary syndrome (PCOS) patients compared with those of the control patients. These results suggested that low expression levels of CD24, prostaglandin synthases and Discussion Cumulus GCs are closely adjacent to the oocyte
Ample results in recent studies have shown the predictive power of some cumulus GC genes for oocyte developmental potential[10,11,12,15]
Summary
Ovarian folliculogenesis is a complex physiological process that underlies the health of the subsequent embryo and offspring[1,2]. Oocyte maturation and ovulation involve multiple intertwined intra-ovarian and endocrine processes[4,5]. Bidirectional somatic granulosa cell-oocyte signaling plays an important role in determining an oocyte’s developmental fate. Considering the bidirectional GC-oocyte signaling, it has been proposed to assess the competence of the oocyte and embryonic development potential by assessing the quality of the GCs. Previous studies indicate that increasing cumulus GC apoptosis is accompanied by impaired oocyte competence and reduced pregnancy outcomes[10,11]. Some investigators have proposed a noninvasive test by scanning gene expression profiles of human cumulus GCs14,15.
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