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

• Published in: PloS one 2014-07, Vol.9 (7), p.e100576
• Main Authors: Yang, Chung-Wei, Chou, Wei-Chun, Chen, Kuan-Hsueh, Cheng, An-Lin, Mao, I-Fang, Chao, How-Ran, Chuang, Chun-Yu
• Format: Article
• Language: English
• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100576

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