Visualized gene network reveals the novel target transcripts Sox2 and Pax6 of neuronal development in trans-placental exposure to bisphenol A

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...

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Veröffentlicht in:PloS one 2014-07, Vol.9 (7), p.e100576
Hauptverfasser: Yang, Chung-Wei, Chou, Wei-Chun, Chen, Kuan-Hsueh, Cheng, An-Lin, Mao, I-Fang, Chao, How-Ran, Chuang, Chun-Yu
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container_title PloS one
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creator Yang, Chung-Wei
Chou, Wei-Chun
Chen, Kuan-Hsueh
Cheng, An-Lin
Mao, I-Fang
Chao, How-Ran
Chuang, Chun-Yu
description 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. 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. 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
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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. 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. 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 &lt;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. 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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. 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. 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 &lt;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. 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25051057</pmid><doi>10.1371/journal.pone.0100576</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2014-07, Vol.9 (7), p.e100576
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1547695967
source MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry
subjects Alcohol
Analysis
Benzhydryl Compounds - toxicity
Biology and Life Sciences
Biomedical engineering
Bisphenol A
Blood
Brain
Cell proliferation
Central Nervous System - drug effects
Central Nervous System - embryology
Children
Cluster analysis
Cord blood
DNA methylation
DNA microarrays
Endocrine disruptors
Endocrine Disruptors - toxicity
Endothelial growth factors
Engineering
Environmental Exposure
Environmental science
Epigenetics
Exposure
Eye Proteins - genetics
Eye Proteins - metabolism
Female
Fetuses
Gene expression
Gene Ontology
Gene Regulatory Networks
Genes
Health aspects
Hedgehog protein
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Hypothesis testing
Insulin
Insulin-like growth factors
Kinases
Maternal-Fetal Exchange
Medicine and Health Sciences
Nervous system diseases
Neurological diseases
Neurons
Notch protein
Paired Box Transcription Factors - genetics
Paired Box Transcription Factors - metabolism
Pax6 protein
PAX6 Transcription Factor
Phenols
Phenols (Class of compounds)
Phenols - toxicity
Placenta
Pregnancy
Pregnant women
Prenatal experience
Prenatal exposure
Repressor Proteins - genetics
Repressor Proteins - metabolism
Rodents
Signaling
SOXB1 Transcription Factors - genetics
SOXB1 Transcription Factors - metabolism
Spinal cord
Stem cells
Transcriptome - drug effects
Umbilical cord
Vascular endothelial growth factor
title Visualized gene network reveals the novel target transcripts Sox2 and Pax6 of neuronal development in trans-placental exposure to bisphenol A
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