Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis.
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.
Women's Reproductive Health Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran. pashaim@tbzmed.ac.ir.|Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. pashaim@tbzmed.ac.ir.|Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. pashaim@tbzmed.ac.ir.
Maryam
M
Pashaiasl
Bioinformatics Research Group and Department of Biology, Qom University, Qom, Iran.
Mansour
M
Ebrahimi
Division of Information Technology, Engineering and the Environment, School of Information Technology and Mathematical Sciences, University of South Australia, Adelaide, Australia.|Institute of Biotechnology, Shiraz University, Shiraz, Iran.|Department of Genetics and Evolution, School of Biological Sciences, The University of Adelaide, Adelaide, Australia.|School of Biological Sciences, Faculty of Science and Engineering, Flinders University, Adelaide, Australia.
Esmaeil
E
Ebrahimie
D005260:Female; D015870:Gene Expression; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000378:metabolism; D065851:Ovarian Reserve / Q000235:genetics*; D060066:Protein Interaction Maps
Biological processes; Diminished ovarian reserve; Granulosa cells; Interaction network; Molecular functions