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Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis

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Abstract

Diminished ovarian reserve (DOR) is one of the reasons for infertility that not only affects both older and young women. Ovarian reserve assessment can be used as a new prognostic tool for infertility treatment decision making. Here, up- and down-regulated gene expression profiles of granulosa cells were analysed to generate a putative interaction map of the involved genes. In addition, gene ontology (GO) analysis was used to get insight intol the biological processes and molecular functions of involved proteins in DOR. Eleven up-regulated genes and nine down-regulated genes were identified and assessed by constructing interaction networks based on their biological processes. PTGS2, CTGF, LHCGR, CITED, SOCS2, STAR and FSTL3 were the key nodes in the up-regulated networks, while the IGF2, AMH, GREM, and FOXC1 proteins were key in the down-regulated networks. MIRN101-1, MIRN153-1 and MIRN194-1 inhibited the expression of SOCS2, while CSH1 and BMP2 positively regulated IGF1 and IGF2. Ossification, ovarian follicle development, vasculogenesis, sequence-specific DNA binding transcription factor activity, and golgi apparatus are the major differential groups between up-regulated and down-regulated genes in DOR. Meta-analysis of publicly available transcriptomic data highlighted the high coexpression of CTGF, connective tissue growth factor, with the other key regulators of DOR. CTGF is involved in organ senescence and focal adhesion pathway according to GO analysis. These findings provide a comprehensive system biology based insight into the aetiology of DOR through network and gene ontology analyses.

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Author information

Authors and Affiliations

  1. Women’s Reproductive Health Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran

    Maryam Pashaiasl

  2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Maryam Pashaiasl

  3. Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Maryam Pashaiasl

  4. Bioinformatics Research Group and Department of Biology, Qom University, Qom, Iran

    Mansour Ebrahimi

  5. Division of Information Technology, Engineering and the Environment, School of Information Technology and Mathematical Sciences, University of South Australia, Adelaide, Australia

    Esmaeil Ebrahimie

  6. Institute of Biotechnology, Shiraz University, Shiraz, Iran

    Esmaeil Ebrahimie

  7. Department of Genetics and Evolution, School of Biological Sciences, The University of Adelaide, Adelaide, Australia

    Esmaeil Ebrahimie

  8. School of Biological Sciences, Faculty of Science and Engineering, Flinders University, Adelaide, Australia

    Esmaeil Ebrahimie

Authors
  1. Maryam Pashaiasl
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  2. Mansour Ebrahimi
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  3. Esmaeil Ebrahimie
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Corresponding author

Correspondence to Maryam Pashaiasl.

Electronic supplementary material

Below is the link to the electronic supplementary material.

11033_2016_4025_MOESM1_ESM.tif

Supplementary material 1 (TIFF 1531 kb). Protein interaction network of up- and down-regulated genes in diminished ovarian reserve (DOR). Network was constructed using one neighbourhood in the expansion algorithm. Interaction between microRNAs and the key genes in diminished ovarian reserve (DOR)

11033_2016_4025_MOESM2_ESM.xlsx

Supplementary material 2 (XLSX 8 kb)Relations between the protein and small molecules in diminished ovarian reserve (DOR).Enriched regulatory subnetworks (p < 0.05) in diminished ovarian reserve (DOR)

Supplementary material 3 (XLSX 15 kb)Relations underlying regulatory sub-networks in diminished ovarian reserve (DOR)

Supplementary material 4 (XLSX 13 kb)Enriched regulatory subnetworks (p < 0.05) in diminished ovarian reserve (DOR)

Supplementary material 5 (XLSX 263 kb)Relations underlying regulatory sub-networks in diminished ovarian reserve (DOR)

Supplementary material 6 (XLSX 23 kb). Relations underlying regulatory sub-networks in diminished ovarian reserve (DOR)

11033_2016_4025_MOESM7_ESM.xlsx

Supplementary material 7 (XLSX 24 kb). Comparative GO analysis of up and down regulated genes in diminished ovarian reserve (DOR) in “Biological Process”

11033_2016_4025_MOESM8_ESM.xlsx

Supplementary material 8 (XLSX 11 kb). Comparative GO analysis of up and down regulated genes in diminished ovarian reserve (DOR) in “Molecular Function”

11033_2016_4025_MOESM9_ESM.xlsx

Supplementary material 9 (XLSX 10 kb). Comparative GO analysis of up and down regulated genes in diminished ovarian reserve (DOR) in “Cellular Components”

11033_2016_4025_MOESM10_ESM.rar

Supplementary material 10 (RAR 36 kb)Meta-analysis of the key regulating genes of in diminished ovarian reserve (DOR), including, PTGS2, CTGF, LHCGR, CITED, SOCS2, STAR and FSTL3, based on co-expression analysis

11033_2016_4025_MOESM11_ESM.xlsx

Supplementary material 11 (XLSX 11 kb). The shared co-expressed genes between the key regulated genes in diminished ovarian reserve (DOR)

11033_2016_4025_MOESM12_ESM.xlsx

Supplementary material 12 (XLSX 81 kb). Regulatory network analysis of control independent dataset. Random samples were taken from whole genes and were subjected to regulatory network analysis

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Pashaiasl, M., Ebrahimi, M. & Ebrahimie, E. Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis. Mol Biol Rep 43, 923–937 (2016). https://doi.org/10.1007/s11033-016-4025-8

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  • DOI: https://doi.org/10.1007/s11033-016-4025-8

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