title: Transcriptomic Changes in Zebrafish Embryos and Larvae Following Benzo[a]pyrene Exposure.
abstract: Benzo[a]pyrene (BaP) is an environmentally relevant carcinogenic and endocrine disrupting compound that causes immediate, long-term, and multigenerational health deficits in mammals and fish. Previously, we found that BaP alters DNA methylation patterns in developing zebrafish, which may affect gene expression. Herein, we performed a genome-wide transcriptional analysis and discovered differential gene expression and splicing in developing zebrafish. Adult zebrafish were exposed to control or 42.0 ± 1.9 µg/l BaP for 7 days. Eggs were collected and raised in control conditions or continuously exposed to BaP until 3.3 and 96 h post-fertilization (hpf). RNA sequencing (RNA-Seq) was conducted on zebrafish embryos and larvae. Data were analyzed to identify differentially expressed (DE) genes (changed at the gene or transcript variant level) and genes with differential exon usage (DEU; changed at the exon level). At 3.3 hpf, BaP exposure resulted in 8 DE genes and 51 DEU genes. At 96 hpf, BaP exposure altered expression in 1153 DE genes and 159 DEU genes. Functional ontology analysis by Ingenuity Pathway Analysis revealed that many disease pathways, including organismal death, growth failure, abnormal morphology of embryonic tissue, congenital heart disease, and adverse neuritogenesis, were significantly enriched for the DE and DEU genes, providing novel insights on the mechanisms of action of BaP-induced developmental toxicities. Collectively, we discovered substantial transcriptomic changes at the gene, transcript variant, and exon levels in developing zebrafish after early life BaP waterborne exposure, and these changes may lead to long-term adverse physiological consequences.
authors.affiliation: *Department of Pediatrics, University of Florida, Gainesville, Florida 32610;
authors.forename: Xiefan
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of BioMolecular Sciences, University of Mississippi, University, Mississippi 38677;
authors.forename: Jone
authors.initials: J
authors.lastname: Corrales
authors.affiliation: Department of BioMolecular Sciences, University of Mississippi, University, Mississippi 38677;
authors.forename: Cammi
authors.initials: C
authors.lastname: Thornton
authors.affiliation: Center for Biotechnology and Genomics, Alcorn State University, Lorman, Mississippi 39096; and.
authors.forename: Tracy
authors.initials: T
authors.lastname: Clerk
authors.affiliation: Genomics and Bioinformatics Research Unit, USDA ARS, Stoneville, Mississippi 38776.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Scheffler
authors.affiliation: Department of BioMolecular Sciences, University of Mississippi, University, Mississippi 38677; kwillett@olemiss.edu.
authors.forename: Kristine L
authors.initials: KL
authors.lastname: Willett
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D005091:Exons; D007814:Larva / Q000187:drug effects* / Q000235:genetics; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D015027:Zebrafish / Q000196:embryology* / Q000254:growth & development
chemical_list: D001564:Benzo(a)pyrene
keywords: RNA-Seq; alternative splicing; benzo[a]pyrene; development; gene expression; zebrafish