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Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development.

Wang XX, Wei JZ, Jiao J, Jiang SY, Yu DH, Li D - Oncotarget (2014)

Bottom Line: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women.Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development.These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

ABSTRACT
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. However, the epigenetic mechanism involved in PCOS progression remains largely unknown. Here, combining the DNA methylation profiling together with transcriptome analysis, we showed that (i) there were 7929 differentially methylated CpG sites (β > 0.1, P < 0.05) and 650 differential transcripts (fold change > 1.5, P < 0.005) in PCOS compared to normal ovaries; (ii) 54 genes were identified with methylated levels that were correlated with gene transcription in PCOS; and (iii) there were less hypermethylated sites, but many more hypomethylated sites residing in CpG islands and N_Shore in PCOS. Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development. These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype. All of this may improve our understanding of the basic molecular mechanism underlying the development of PCOS.

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GO analysis of the differentially methylated and expressed genesA, GO analysis of differential methylated genes (β > 0.1, P < 0.05). B, GO analysis of differential expressed genes (fold change > 1.5, P < 0.005). X axis, negative logarithm (-lg) of the p value; Y axis, GO category. The top 10 GO terms were shown if there were more than 10 terms.
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Figure 2: GO analysis of the differentially methylated and expressed genesA, GO analysis of differential methylated genes (β > 0.1, P < 0.05). B, GO analysis of differential expressed genes (fold change > 1.5, P < 0.005). X axis, negative logarithm (-lg) of the p value; Y axis, GO category. The top 10 GO terms were shown if there were more than 10 terms.

Mentions: To begin defining the functional significance of the extensive changes in DNA methylation and gene expression profiling of PCOS, GO analysis was performed, which revealed distinct functional categories for the PCOS-associated gene lists (Supplementary Table 3). As shown in Fig. 2A, these differentially methylated genes were widely associated with cell adhesion, the regulation of GTPase activity, neuron differentiation, synapse organization, skeletal system development and extracellular structure organization. In addition, differentially expressed genes were found to be highly involved in basal cellular processes like the regulation of transcription, cell death, apoptosis, cell proliferation, and response to stress, endogenous stimuli, hormone stimuli and organic substances (Fig. 2B).


Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development.

Wang XX, Wei JZ, Jiao J, Jiang SY, Yu DH, Li D - Oncotarget (2014)

GO analysis of the differentially methylated and expressed genesA, GO analysis of differential methylated genes (β > 0.1, P < 0.05). B, GO analysis of differential expressed genes (fold change > 1.5, P < 0.005). X axis, negative logarithm (-lg) of the p value; Y axis, GO category. The top 10 GO terms were shown if there were more than 10 terms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196149&req=5

Figure 2: GO analysis of the differentially methylated and expressed genesA, GO analysis of differential methylated genes (β > 0.1, P < 0.05). B, GO analysis of differential expressed genes (fold change > 1.5, P < 0.005). X axis, negative logarithm (-lg) of the p value; Y axis, GO category. The top 10 GO terms were shown if there were more than 10 terms.
Mentions: To begin defining the functional significance of the extensive changes in DNA methylation and gene expression profiling of PCOS, GO analysis was performed, which revealed distinct functional categories for the PCOS-associated gene lists (Supplementary Table 3). As shown in Fig. 2A, these differentially methylated genes were widely associated with cell adhesion, the regulation of GTPase activity, neuron differentiation, synapse organization, skeletal system development and extracellular structure organization. In addition, differentially expressed genes were found to be highly involved in basal cellular processes like the regulation of transcription, cell death, apoptosis, cell proliferation, and response to stress, endogenous stimuli, hormone stimuli and organic substances (Fig. 2B).

Bottom Line: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women.Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development.These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

ABSTRACT
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. However, the epigenetic mechanism involved in PCOS progression remains largely unknown. Here, combining the DNA methylation profiling together with transcriptome analysis, we showed that (i) there were 7929 differentially methylated CpG sites (β > 0.1, P < 0.05) and 650 differential transcripts (fold change > 1.5, P < 0.005) in PCOS compared to normal ovaries; (ii) 54 genes were identified with methylated levels that were correlated with gene transcription in PCOS; and (iii) there were less hypermethylated sites, but many more hypomethylated sites residing in CpG islands and N_Shore in PCOS. Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development. These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype. All of this may improve our understanding of the basic molecular mechanism underlying the development of PCOS.

Show MeSH
Related in: MedlinePlus