Dataset Information

Identification of Polycystic Ovary Syndrome (PCOS) Specific Genes in Cumulus and Mural Granulosa Cells.

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.

SUBMITTER: Aydos A

PROVIDER: S-EPMC5173369 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Identification of Polycystic Ovary Syndrome (PCOS) Specific Genes in Cumulus and Mural Granulosa Cells.

Aydos Alp A Gurel Aykut A Oztemur Islakoglu Yasemin Y Noyan Senem S Gokce Bagdagul B Ecemis Tolga T Kaya Cemil C Aksu Arif Tarik AT Gur Dedeoglu Bala B

PloS one 20161220 12

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 ...[more]

PMID: 27997581

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Project description:PCOS is a complex genetic disease reflecting the interplay of susceptibility genes and environmental factors. The cardinal reproductive feature of the syndrome, hyperandrogenemia, appears to play a direct role in the pathogenesis of the associated metabolic abnormalities. Male as well as female first-degree relatives have reproductive and metabolic phenotypes including increased prevalence rates of type 2 diabetes (T2D), metabolic syndrome (MBS) and other risk factors for cardiovascular disease (CVD). Northwestern University (NU) investigators lead a team that has extensive experience in phenotyping PCOS and in the genetic analysis of complex diseases including genome-wide association study (GWAS). Together with an expert group of collaborators from the Hershey Medical Center, and The University of Chicago, we have conducted a GWAS to identify PCOS susceptibility alleles using a large cohort of extensively and consistently phenotyped PCOS cases. Population controls for this study come from the NUgene project described below. NUgene project: In 2002, Northwestern committed to the development of a DNA repository to serve as a platform for the identification and validation of genotype-phenotype associations that will impact healthcare. The NUgene Project is a repository with longitudinal medical information from participating patients at affiliated hospitals and outpatient clinics from the Northwestern University Medical Center. Participants' DNA samples are coupled with data from a questionnaire (2 versions were used, 1 before and 1 after February 2006, both are included) and continuously updated data from our Electronic Medical Record (EMR) representing actual clinical care events. Northwestern has a state-of-the art, comprehensive inpatient and outpatient EMR system of over 2 million patients. NUgene has broad access to participant data for all outpatient visits as well as inpatient data via a consolidated data warehouse. NUgene participants consent to distribution and use of their coded DNA samples and data for a broad range of genetic research by third-party investigators.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrine abnormalities in women of reproductive age. In this study, we set out to construct a molecular long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network according to the competitive endogenous RNA (ceRNA) theory and obtain insights into the related biological characteristics and pathways.MethodsWe downloaded two gene expression profile datasets of mural granulosa cells (MGCs) of women with PCOS and healthy women without PCOS (GSE84376 and GSE106724) from Gene Expression Omnibus (GEO) DataSets. Using GEO2R, we identified the mRNAs and non-coding RNAs with differential expression. The DIANA-microT-CDS algorithm was applied to predict the genes targeted by the differentially expressed miRNAs. The lncRNA-miRNA interactions were predicted using DIANA-LncBase v2. Then, we constructed the lncRNA-miRNA-mRNA network. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was employed to identify the functions and enriched pathways of the genes. Subsequently, STRING was used to construct the protein-protein interaction (PPI) network. cytoHubba in Cytoscape was used to rank the hub genes, and finally, PPI modules were screened with Cytoscape MCODE.ResultsThere were 462 mRNAs, 2,464 lncRNAs, and 55 miRNAs which showed differential expression between the MGCs of patients with PCOS and those of healthy controls. Based on the PPI analysis, differentially expressed genes (DEGs) were significantly enriched in retinol metabolism, drug metabolism-cytochrome P450, malaria, the Hippo signaling pathway, and glycine, serine, and threonine metabolism. The ceRNA network contained 71 lncRNA nodes, 14 miRNA nodes, and 69 mRNA nodes, as well as 167 edges. We identified some novel genes and non-coding RNAs that might be involved in PCOS, including CD163, MRC1, VSIG4, CCL2, CCR2, SPP1, hsa-miR-3135b, hsa-miR-4649-3p, hsa-miR-1231, hsa-miR-3609, and hsa-miR-4433b-3p.ConclusionsThis study identified a novel lncRNA-miRNA-mRNA network based on the ceRNA mechanism in PCOS. Some novel genes and non-coding RNAs that may be involved in the occurrence and development of PCOS were excavated, including CD163, MRC1, VSIG4, CCL2, CCR2, SPP1, hsa-miR-3135b, hsa-miR-4649-3p, hsa-miR-1231, hsa-miR-3609, and hsa-miR-4433b-3p. However, our findings need to be validated by in vivo and in vitro experiments.

Dataset Information

Identification of Polycystic Ovary Syndrome (PCOS) Specific Genes in Cumulus and Mural Granulosa Cells.

Publications

Identification of Polycystic Ovary Syndrome (PCOS) Specific Genes in Cumulus and Mural Granulosa Cells.

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