Dataset Information

Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome.

ABSTRACT: The present study aimed to identify potentially important biomarkers associated with polycystic ovary syndrome (PCOS) by integrating DNA methylation with transcriptome profiling. The transcription (E?MTAB?3768) and methylation (E?MTAB?3777) datasets were retrieved from ArrayExpress. Paired transcription and methylation profiling data of 10 cases of PCOS and 10 healthy controls were available for screening differentially expressed genes (DEGs) and differentially methylated genes (DMGs). Genes with a negative correlation between expression levels and methylation levels were retained by correlation analysis to construct a protein?protein interaction (PPI) network. Subsequently, functional and pathway enrichment analyses were performed to identify genes in the PPI network. Additionally, a disease?associated pathway network was also established. A total of 491 overlapping genes, and the expression levels of 237 genes, were negatively correlated with their methylation levels. Functional enrichment analysis revealed that genes in the PPI network were mainly involved with biological processes of cellular response to stress, negative regulation of the biosynthetic process, and regulation of cell proliferation. The constructed pathway network associated with PCOS led to the identification of four important genes (SPP1, F2R, IL12B and RBP4) and two important pathways (Jak?STAT signaling pathway and neuroactive ligand?receptor interaction). Taken, together, the results from the present study have revealed numerous important genes with abnormal DNA methylation levels and altered mRNA expression levels, along with their associated functions and pathways. These findings may contribute to an improved understanding of the possible pathophysiology of PCOS.

SUBMITTER: Liu L

PROVIDER: S-EPMC7115196 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome.

Liu Li L He Dongyun D Wang Yang Y Sheng Minjia M

Molecular medicine reports 20200226 5

The present study aimed to identify potentially important biomarkers associated with polycystic ovary syndrome (PCOS) by integrating DNA methylation with transcriptome profiling. The transcription (E‑MTAB‑3768) and methylation (E‑MTAB‑3777) datasets were retrieved from ArrayExpress. Paired transcription and methylation profiling data of 10 cases of PCOS and 10 healthy controls were available for screening differentially expressed genes (DEGs) and differentially methylated genes (DMGs). Genes wit ...[more]

PMID: 32323770

Similar Datasets

Project description:BackgroundWomen with polycystic ovary syndrome (PCOS) manifest a host of ovarian defects like impaired folliculogenesis, anovulation, and poor oocyte quality, which grossly affect their reproductive health. Addressing the putative epigenetic anomalies that tightly regulate these events is of foremost importance in this disorder. We therefore aimed to carry out DNA methylome profiling of cumulus granulosa cells and assess the methylation and transcript expression profiles of a few differentially methylated genes contributing to ovarian defects in PCOS. A total of 20 controls and 20 women with PCOS were selected from a larger cohort of women undergoing IVF, after carefully screening their sera and follicular fluids for hormonal and biochemical parameters. DNA extracted from cumulus granulosa cells of three women each, from control and PCOS groups was subjected to high-throughput, next generation bisulfite sequencing, using the Illumina HiSeq 2500® platform. Remaining samples were used for the validation of methylation status of some identified genes by pyrosequencing, and the transcript expression profiles of these genes were assessed by quantitative real-time PCR.ResultsIn all, 6486 CpG sites representing 3840 genes associated with Wnt signaling, G protein receptor, endothelin/integrin signaling, angiogenesis, chemokine/cytokine-mediated inflammation, etc., showed differential methylation in PCOS. Hypomethylation was noted in 2977 CpGs representing 2063 genes while 2509 CpGs within 1777 genes showed hypermethylation. Methylation differences were also noted in noncoding RNAs regulating several ovarian functions that are dysregulated in PCOS. Few differentially methylated genes such as aldo-keto reductase family 1 member C3, calcium-sensing receptor, resistin, mastermind-like domain 1, growth hormone-releasing hormone receptor and tumor necrosis factor, which predominantly contribute to hyperandrogenism, premature luteolysis, and oocyte development defects, were explored as novel epigenetic candidates in mediating ovarian dysfunction. Methylation profiles of these genes matched with our NGS findings, and their transcript expression patterns correlated with the gene hypo- or hypermethylation status.ConclusionOur findings suggest that the epigenetic dysregulation of genes involved in important processes associated with follicular development may contribute to ovarian defects observed in women with PCOS.

Project description:Polycystic ovary syndrome (PCOS) is typically characterized by a polycystic ovarian morphology, hyperandrogenism, ovulatory dysfunction, and infertility. Furthermore, PCOS patients undergoing ovarian stimulation have more oocytes; however, the poor quality of oocytes leads to lower fertilization and implantation rates, decreased pregnancy rates, and increased miscarriage rates. The complex molecular mechanisms underlying PCOS and the poor quality of oocytes remain to be elucidated. We obtained matched oocytes and cumulus cells (CCs) from PCOS patients, compared them with age-matched controls, and performed RNA sequencing analysis to explore the transcriptional characteristics of their oocytes and CCs. Moreover, we validated our newly confirmed candidate genes for PCOS by immunofluorescence. Unsupervised clustering analysis showed that the overall global gene expression patterns and transposable element (TE) expression profiles of PCOS patients tightly clustered together, clearly distinct from those of controls. Abnormalities in functionally important pathways are found in PCOS oocytes. Notably, genes involved in microtubule processes, TUBB8 and TUBA1C, are overexpressed in PCOS oocytes. The metabolic and oxidative phosphorylation pathways are also dysregulated in both oocytes and CCs from PCOS patients. Moreover, in oocytes, differentially expressed TEs are not uniformly dispersed in human chromosomes. Endogenous retrovirus 1 (ERV1) elements located on chromosomes 2, 3, 4, and 5 are rather highly upregulated. Interestingly, these correlate with the most highly expressed protein-coding genes, including tubulin-associated genes TUBA1C, TUBB8P8, and TUBB8, linking the ERV1 elements to the occurrence of PCOS. Our comprehensive analysis of gene expression in oocytes and CCs, including TE expression, revealed the specific molecular features of PCOS. The aberrantly elevated expression of TUBB8 and TUBA1C and ERV1 provides additional markers for PCOS and may contribute to the compromised oocyte developmental competence in PCOS patients. Our findings may also have implications for treatment strategies to improve oocyte maturation and the pregnancy outcomes for women with PCOS.

Dataset Information

Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome.

Publications

Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets