title: Visualized gene network reveals the novel target transcripts Sox2 and Pax6 of neuronal development in trans-placental exposure to bisphenol A.
abstract: BACKGROUND
  Bisphenol A (BPA) is a ubiquitous endocrine disrupting chemical in our daily life, and its health effect in response to prenatal exposure is still controversial. Early-life BPA exposure may impact brain development and contribute to childhood neurological disorders. The aim of the present study was to investigate molecular target genes of neuronal development in trans-placental exposure to BPA.
  
  
  METHODS
  A meta-analysis of three public microarray datasets was performed to screen for differentially expressed genes (DEGs) in exposure to BPA. The candidate genes of neuronal development were identified from gene ontology analysis in a reconstructed neuronal sub-network, and their gene expressions were determined using real-time PCR in 20 umbilical cord blood samples dichotomized into high and low BPA level groups upon the median 16.8 nM.
  
  
  RESULTS
  Among 36 neuronal transcripts sorted from DAVID ontology clusters of 457 DEGs using the analysis of Bioconductor limma package, we found two neuronal genes, sex determining region Y-box 2 (Sox2) and paired box 6 (Pax6), had preferentially down-regulated expression (Bonferroni correction p-value <10(-4) and log2-transformed fold change ≤-1.2) in response to BPA exposure. Fetal cord blood samples had the obviously attenuated gene expression of Sox2 and Pax6 in high BPA group referred to low BPA group. Visualized gene network of Cytoscape analysis showed that Sox2 and Pax6 which were contributed to neural precursor cell proliferation and neuronal differentiation might be down-regulated through sonic hedgehog (Shh), vascular endothelial growth factor A (VEGFA) and Notch signaling.
  
  
  CONCLUSIONS
  These results indicated that trans-placental BPA exposure down-regulated gene expression of Sox2 and Pax6 potentially underlying the adverse effect on childhood neuronal development.
authors: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors: Chung-Wei
authors: CW
authors: Yang
authors: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors: Wei-Chun
authors: WC
authors: Chou
authors: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors: Kuan-Hsueh
authors: KH
authors: Chen
authors: Schools of Nursing and Health Studies, University of Missouri-Kansas City, Kansas City, Kansas, United States of America.
authors: An-Lin
authors: AL
authors: Cheng
authors: School of Occupational Safety and Health, Chung Shan Medical University, Taichung, Taiwan.
authors: I-Fang
authors: IF
authors: Mao
authors: Emerging Compounds Research Center, Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Pingtung County, Taiwan.
authors: How-Ran
authors: HR
authors: Chao
authors: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors: Chun-Yu
authors: CY
authors: Chuang
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D002490:Central Nervous System / Q000187:drug effects / Q000196:embryology; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008431:Maternal-Fetal Exchange; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010636:Phenols; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C000605730:PAX6 protein, human; C527782:SOX2 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds