title: Transcriptomic Responses During Early Development Following Arsenic Exposure in Western Clawed Frogs, Silurana tropicalis.
abstract: Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development.
authors.affiliation: *Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada, K7K 7B4;
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: *Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada, K7K 7B4;
authors.forename: Iris
authors.initials: I
authors.lastname: Koch
authors.affiliation: *Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada, K7K 7B4;
authors.forename: Laura A
authors.initials: LA
authors.lastname: Gibson
authors.affiliation: University of New Brunswick and Canadian River Institute, NB, Canada, E2L 4L5;
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Loughery
authors.affiliation: University of New Brunswick and Canadian River Institute, NB, Canada, E2L 4L5; Center for Environmental and Human Toxicology & Department of Physiological Sciences, UF Genetics Institute, University of Florida, Gainesville, Florida 32611; and.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martyniuk
authors.affiliation: *Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada, K7K 7B4;
authors.forename: Mark
authors.initials: M
authors.lastname: Button
authors.affiliation: *Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada, K7K 7B4;
authors.forename: Guilhem
authors.initials: G
authors.lastname: Caumette
authors.affiliation: *Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada, K7K 7B4;
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Reimer
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, BC, Canada, V6T 1Z1.
authors.forename: William R
authors.initials: WR
authors.lastname: Cullen
authors.affiliation: *Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada, K7K 7B4; valerie.langlois@rmc.ca.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Langlois
mesh_terms: D000818:Animals; D001149:Arsenates / Q000378:metabolism / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D019295:Computational Biology; D030541:Databases, Genetic; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D007814:Larva / Q000187:drug effects / Q000235:genetics; D013058:Mass Spectrometry; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*; D014981:Xenopus / Q000196:embryology / Q000235:genetics* / Q000378:metabolism
chemical_list: D001149:Arsenates; C009277:sodium arsenate
keywords: amphibians; arsenate; gene ontology; gene set enrichment; pathway analysis