The transcriptome of corona radiata cells from individual MІІ oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

Abstract

BackgroundCorona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility. It is controversial whether PCOS associate with diminished oocyte quality. The purpose of this study was to compare individual human CRC samples between PCOS patients and controls.MethodsAll patients were stimulated by the long gonadotropin-releasing hormone (GnRH) agonist protocol. The CRC samples originated from individual oocytes developing into embryos selected for transfer. CRCs were isolated in a two-step denudation procedure, separating outer cumulus cells from the inner CRCs. Extracted RNA was amplified and transcriptome profiling was performed with Human Agilent® arrays.ResultsThe transcriptomes of CRCs showed no individual genes with significant differential expression between PCOS and controls, but gene set enrichment analysis identified several cell cycle- and DNA replication pathways overexpressed in PCOS CRCs (FDR < 0.05). Five of the genes contributing to the up-regulated cell cycle pathways in the PCOS CRCs were selected for qRT-PCR validation in ten PCOS and ten control CRC samples. qRT-PCR confirmed significant up-regulation in PCOS CRCs of cell cycle progression genes HIST1H4C (FC = 2.7), UBE2C (FC = 2.6) and cell cycle related transcription factor E2F4 (FC = 2.5).ConclusionThe overexpression of cell cycle-related genes and cell cycle pathways in PCOS CRCs could indicate a disturbed or delayed final maturation and differentiation of the CRCs in response to the human chorionic gonadotropin (hCG) surge. However, this had no effect on the in vitro development of the corresponding embryos. Future studies are needed to clarify whether the up-regulated cell cycle pathways in PCOS CRCs have any clinical implications.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-014-0110-6) contains supplementary material, which is available to authorized users.

Influence of follicular fluid and cumulus cells on oocyte quality: clinical implications

“…Wo m e n w i t h P C O S s e e m t o u n d e rg o a l t e r e d folliculogenesis with arrested small follicles; they can also exhibit an altered follicular hormonal environment [181][182][183], which may interfere with oocyte maturation, metabolism, and competence acquisition. Altered expressions of various transcripts, such as those encoding insulin receptors [175], IGF-binding proteins and receptors [184], and genes related to meiotic cell cycle regulation [185] have been observed in CCs from women with PCOS, suggesting that these women experience disturbances or delays in CC maturation and differentiation [185] and/or compromises in CC function [175]. Other studies focusing on CCs from these women found changes in long noncoding RNAs (lncRNAs; e.g., XLOC_011402, ENST00000454271, ENST00000433673, ENST00000450294, and ENST00000432431) [7], miRNAs (17 were differentially expressed; hsa-miRNA-135b-5p was the most highly upregulated and hsa-miRNA-3940-5p was the only example of downregulation) [186,187], and the methylation patterns of specific gene [188] when compared to controls, indicating that these cells undergo epigenetic deregulation.…”

Molecular Features of Polycystic Ovary Syndrome Revealed by Transcriptome Analysis of Oocytes and Cumulus Cells

“…Most of previous studies on PCOS focused on ovarian somatic cells, peripheral blood, or other cell types – for instance, CCs of PCOS patients display abnormal characteristics of gene expression, including dysregulated growth factors, steroid metabolism, cell cycle, steroid hormone biosynthesis, and hypomethylated genes related to the synthesis of lipid and steroid ( Haouzi et al, 2012 ; Wissing et al, 2014 ; Liu et al, 2016 ; Pan et al, 2018 ). Dysregulation of inflammatory function has also been found in PCOS patients through transcriptome and DNA methylation analysis of peripheral blood and granulosa-lutein cells ( Adams et al, 2016 ; Su et al, 2018 ; Hiam et al, 2019 ).…”

“…These studies facilitated an understanding of the etiologic factors accounting for PCOS. Microarray or RNA sequencing analysis of oocytes and/or granulosa cells or cumulus cells (CCs) in women with PCOS has provided insights into the understanding of PCOS ( Wood et al, 2007 ; Haouzi et al, 2012 ; Wissing et al, 2014 ; Liu et al, 2016 ; Chen et al, 2019 ). In addition, studies focused on ovarian somatic cells or ovary and other tissues revealed the metabolic abnormalities in PCOS ( Ma et al, 2007 ; Corton et al, 2008 ; Huang et al, 2010 ; Zhao et al, 2017 ; Sanchez-Garrido and Tena-Sempere, 2020 ).…”

Comprehensive molecular features of polycystic ovary syndrome revealed by transcriptome analysis of oocytes and cumulus cells

“…Most of previous studies on PCOS focused on ovarian somatic cells, peripheral blood or other cell types. For instance, cumulus cells of PCOS patients display abnormal characteristics of gene expression including dysregulated growth factors, steroid metabolism, cell cycle, steroid hormone biosynthesis and hypomethylated genes related to the synthesis of lipid and steroid 7–9,46 . Dysregulation of inflammatory function also has been found in PCOS patients through transcriptome and DNA methylation analysis of peripheral blood and granulosa-lutein cells 47–49 .…”