Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 May 21;8(5):e64801.
doi: 10.1371/journal.pone.0064801. Print 2013.

Genome-wide methylated DNA immunoprecipitation analysis of patients with polycystic ovary syndrome

Hao-Ran Shen  1 , Li-Hua Qiu, Zhi-Qing Zhang, Yuan-Yuan Qin, Cong Cao, Wen Di
Affiliations

Genome-wide methylated DNA immunoprecipitation analysis of patients with polycystic ovary syndrome

Hao-Ran Shen et al. PLoS One. .

Abstract

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous disorder of uncertain etiology. Recent studies suggested that insulin resistance (IR) plays an important role in the development of PCOS. In the current study, we aimed to investigate the molecular mechanism of IR in PCOS. We employed genome-wide methylated DNA immunoprecipitation (MeDIP) analysis to characterize genes that are differentially methylated in PCOS patients vs. healthy controls. Besides, we also identified the differentially methylated genes between patients with PCOS-non-insulin resistance (PCOS-NIR) and PCOS-insulin resistance (PCOS-IR). A total of 79 genes were differentially methylated between PCOS-NIR vs. PCOS-IR patients, and 40 genes were differentially methylated in PCOS patients vs. healthy controls. We analyzed these differentially methylated genes by constructing regulatory networks and protein-protein interaction (PPI) networks. Further, Gene Ontology (GO) and pathway enrichment analysis were also performed to investigate the biological functions of networks. We identified multiple categories of genes that were differentially methylated between PCOS-NIR and PCOS-IR patients, or between PCOS patients and healthy controls. Significantly, GO categories of immune response were differentially methylated in PCOS-IR vs. PCOS-NIR. Further, genes in cancer pathways were also differentially methylated in PCOS-NIR vs. PCOS-IR patients or in PCOS patients vs. healthy controls. The results of this current study will help to further understand the mechanism of PCOS.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. MS-PCR electrophoretogram showing the specificity of methylated DNA.
Bands in the M lanes represent the methylated PCR products of ER-β, whereas bands in the U lanes represent the unmethylated ER-β. The presence of a 250 bp band indicates hypermethylated DNA fragment and the fuzzy band in the U lane indicates partially methylated DNA fragment.
Figure 2
Figure 2. Regulatory network analysis of differentially methylated genes.
A. regulatory network of differentially methylated genes between PCOS-NIR and PCOS-IR patients; B. regulatory network of differentially methylated genes between PCOS patients and healthy controls. The yellow nodes represent methylated genes and pink nodes represent normal genes.
Figure 3
Figure 3. Protein-protein interaction (PPI) network analysis.
A. Protein-protein interaction (PPI) network of PCOS-NIR and PCOS-IR; B. PPI network of PCOS and controls. Yellow nodes represent methylated genes and pink nodes represent normal genes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Fauser B, Diedrich K, Bouchard P, Domínguez F, Matzuk M, et al. (2011) Contemporary genetic technologies and female reproduction. Human reproduction update 17: 829–847. - PMC - PubMed
    1. Legro RS, Strauss JF (2002) Molecular progress in infertility: polycystic ovary syndrome. Fertility and sterility 78: 569–576. - PubMed
    1. Diamanti-Kandarakis E, Kandarakis H, Legro RS (2006) The role of genes and environment in the etiology of PCOS. Endocrine 30: 19–26. - PubMed
    1. Hickey TE, Legro RS, Norman RJ (2006) Epigenetic modification of the X chromosome influences susceptibility to polycystic ovary syndrome. J Clin Endocrinol Metab 91: 2789–2791. - PubMed
    1. van Houten E, Mcluskey A, Kramer P, Karels B, Themmen A, et al... (2011) Development of a mouse model with polycystic ovary syndrome. pp. P94.

Publication types

Substances

Grants and funding

This work was supported by grants from the International Collaborative Items of Ministry of Science and Technology of China (No. 2006DFA32780). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.