The differential transcriptome and ontology profiles of floating and cumulus granulosa cells in stimulated human antral follicles

Abstract

Communication between various ovarian cell types is a prerequisite for folliculogenesis and ovulation. In antral follicles granulosa cells divide into two distinct populations of mural and cumulus granulosa cells (CGC), enveloping the antrum and surrounding the oocyte, respectively. Both cell types, with the mural compartment in excess, contribute to the floating granulosa cell (FGC) population in the follicular fluid. The aim of this study was to compare the transcriptomes of FGC and CGC in stimulated antral follicles obtained from 19 women undergoing IVF-ICSI procedure. FGC were obtained from follicular fluid during the follicle puncture procedure and CGC were acquired after oocyte denudation for micromanipulation. Gene expression analysis was conducted using the genome-wide Affymetrix transcriptome array. The expression profile of the two granulosa cell populations varied significantly. Out of 28 869 analysed transcripts 4480 were differentially expressed (q-value < 10(-4)) and 489 showed > or =2-fold difference in the expression level with 222 genes up-regulated in FGC and 267 in CGC. The transcriptome of FGC showed higher expression of genes involved in immune response, hematological system function and organismal injury, although CGC had genes involved in protein degradation and nervous system function up-regulated. Cell-to-cell signalling and interaction pathways were noted in both cell populations. Furthermore, numerous novel transcripts that have not been previously described in follicular physiology were identified. In conclusion, our results provide a solid basis for future studies in follicular biology that will help to identify molecular markers for oocyte and embryo viability in IVF.

Female Aging Alters Expression of Human Cumulus Cells Genes that Are Essential for Oocyte Quality

“…Cytokines are important in the regulation of ovarian function and oocyte quality [25]. On the other hand interleukins IL18 and IL1 β were reported to be present in floating granulosa cells of human preovulatory follicles [26]. CC median group may be characterized by an overexpression of gene members of the “insulin-signaling pathway”, such as IGFBP3 and IGFBP5 whereas INSR was overexpressed in both the CC median and CC older groups.…”

“…However, it may be associated with pathology and induced by microenvironmental factors like hypoxia. In this context, the follicular cells synthesize several angiogenic factors [26, 35, 36], among which the vascular endothelial growth factor C ( VEGFC ) and angiopoietin-like 4 ( ANGPTL4 ), which are induced in response to hypoxic stimuli [37–39]. So, the overexpression of angiogenic factors and hypoxia-inducible protein 2 ( HIG2 ) in the CC older group could be caused by insufficiency of oxygen.…”

Gene expression profiling of granulosa cells from PCOS patients following varying doses of human chorionic gonadotropin

“…These observations were further supported by subsequent studies that measured global gene expression of cumulus cells, which was concluded to be a non-invasive test for oocyte/embryo quality [2,3,15,41]. Granulosa and cumulus cell gene expression profiling has also been used to compare the effects of recombinant FSH vs. human menopausal gonadotrophin (hMG) [6,14], floating vs. cumulus granulosa cells [22], cumulus cells from lean vs. overweight-obese PCOS patients [21], and ovarian reserve status in young women with diminished ovarian reserve [39].…”

Granulosa cell biomarkers to predict pregnancy in ART: pieces to solve the puzzle

“…When comparing CC to MGC, more than 1500 RNAs varied by ≥2-fold between the two cell types. A third study examined MGC and CC samples from mature oocytes (Burnik et al 2015b) and conducted a meta-analysis with the data generated from the previous two studies ( Koks et al 2010, Grondahl et al 2012. When genes with log 2 fold-change ≥2 were evaluated collectively, 3156 genes were differentially expressed.…”