Abstract
Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disorder which affects women of reproductive age with prevalence of 8–18%. The oocyte within the follicle is surrounded by cumulus cells (CCs), which connect with mural granulosa cells (MGCs) that are responsible for secreting steroid hormones. The main aim of this study is comparing gene expression profiles of MGCs and CCs in PCOS and control samples to identify PCOS-specific differentially expressed genes (DEGs). In this study, two microarray databases were searched for mRNA expression microarray studies performed with CCs and MGCs obtained from PCOS patients and control samples. Three independent studies were selected to be integrated with naive meta-analysis since raw meta-data from these studies were found to be highly correlated. DEGs in these somatic cells were identified for PCOS and control groups. This study enabled us to reveal dysregulation in MAPK (mitogen activated protein kinase), insulin and Wnt signaling pathways between CCs and MGCs in PCOS. The meta-analysis results together with qRT-PCR validations provide evidence that molecular signaling is dysregulated through MGCs and CCs in PCOS, which is important for follicle and oocyte maturation and may contribute to the pathogenesis of the syndrome.
Highlights
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age [1]
Applying our search filtering criteria, we found three microarray datasets (GSE10946, GSE34526 and E-MEXP-3641) that had been performed with Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays
Since 37 of the PCOS-specific differentially expressed genes (DEGs) were enriched in the MAPK signaling pathway (S2 Fig), we focused on those genes that are members of this pathway to perform further analysis
Summary
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age [1]. The syndrome has heterogeneous clinical characteristics, including hyperandrogenemia, ovulatory dysfunction, polycystic ovarian morphology (PCOM) and metabolic disorders (obesity, insulin resistance and diabetes). It is a common cause of anovulation and female infertility through impairing oocyte-follicle maturation [2]. Mural granulosa cells (MGCs) and cumulus cells (CCs), which are the somatic cells that make up the oocyte microenvironment, secrete steroid hormones and produce growth. Identification of PCOS Specific Genes in Cumulus and Mural Granulosa Cells the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section
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