PMID- 29929084 OWN - NLM STAT- MEDLINE DCOM- 20180817 LR - 20181202 IS - 1879-1514 (Electronic) IS - 0166-445X (Linking) VI - 201 DP - 2018 Aug TI - RNA-Seq analysis of transcriptome responses in Atlantic cod (Gadus morhua) precision-cut liver slices exposed to benzo[a]pyrene and 17alpha-ethynylestradiol. PG - 174-186 LID - S0166-445X(18)30521-6 [pii] LID - 10.1016/j.aquatox.2018.06.003 [doi] AB - Polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) that activate the aryl hydrocarbon receptor (Ahr) pathway, and endocrine disruptors acting through the estrogen receptor pathway are among environmental pollutants of major concern. In this work, we exposed Atlantic cod (Gadus morhua) precision-cut liver slices (PCLS) to BaP (10 nM and 1000 nM), ethynylestradiol (EE2) (10 nM and 1000 nM), and equimolar mixtures of BaP and EE2 (10 nM and 1000 nM) for 48 h, and performed RNA-Seq based transcriptome mapping followed by systematic bioinformatics analyses. Our gene expression analysis showed that several genes were differentially expressed in response to BaP and EE2 treatments in PCLS. Strong up-regulation of genes coding for the cytochrome P450 1a (Cyp1a) enzyme and the Ahr repressor (Ahrrb) was observed in BaP treated PCLS. EE2 treatment of liver slices strongly up-regulated genes coding for precursors of vitellogenin (Vtg) and eggshell zona pellucida (Zp) proteins. As expected, pathway enrichment and network analysis showed that the Ahr and estrogen receptor pathways are among the top affected by BaP and EE2 treatments, respectively. Interestingly, two genes coding for fibroblast growth factor 3 (Fgf3) and fibroblast growth factor 4 (Fgf4) were up-regulated by EE2 in this study. To our knowledge, the fgf3 and fgf4 genes have not previously been described in relation to estrogen signaling in fish liver, and these results suggest the modulation of the FGF signaling pathway by estrogens in fish. The signature expression profiles of top differentially expressed genes in response to the single compound (BaP or EE2) treatment were generally maintained in the expression responses to the equimolar binary mixtures. However, in the mixture-treated groups, BaP appeared to have anti-estrogenic effects as observed by lower number of differentially expressed putative EE2 responsive genes. Our in-depth quantitative analysis of changes in liver transcriptome in response to BaP and EE2, using PCLS tissue culture provides further mechanistic insights into effects of the compounds. Moreover, the analyses demonstrate the usefulness of PCLS in cod for omics experiments. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Yadetie, Fekadu AU - Yadetie F AD - Department of Biological Sciences, University of Bergen, Bergen, Norway. Electronic address: Fekadu.Yadetie@uib.no. FAU - Zhang, Xiaokang AU - Zhang X AD - Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway. Electronic address: Xiaokang.Zhang@uib.no. FAU - Hanna, Eileen Marie AU - Hanna EM AD - Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway. Electronic address: Eileen.Hanna@uib.no. FAU - Aranguren-Abadia, Libe AU - Aranguren-Abadia L AD - Department of Biological Sciences, University of Bergen, Bergen, Norway. Electronic address: Libe.Aranguren@uib.no. FAU - Eide, Marta AU - Eide M AD - Department of Biological Sciences, University of Bergen, Bergen, Norway. Electronic address: Marta.Eide@uib.no. FAU - Blaser, Nello AU - Blaser N AD - Department of Mathematics, University of Bergen, Bergen, Norway. Electronic address: Nello.Blaser@uib.no. FAU - Brun, Morten AU - Brun M AD - Department of Mathematics, University of Bergen, Bergen, Norway. Electronic address: Morten.Brun@uib.no. FAU - Jonassen, Inge AU - Jonassen I AD - Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway. Electronic address: Inge.Jonassen@uib.no. FAU - Goksoyr, Anders AU - Goksoyr A AD - Department of Biological Sciences, University of Bergen, Bergen, Norway. Electronic address: Anders.Goksoyr@uib.no. FAU - Karlsen, Odd Andre AU - Karlsen OA AD - Department of Biological Sciences, University of Bergen, Bergen, Norway. Electronic address: Odd.Karlsen@uib.no. LA - eng PT - Journal Article DEP - 20180607 PL - Netherlands TA - Aquat Toxicol JT - Aquatic toxicology (Amsterdam, Netherlands) JID - 8500246 RN - 0 (Water Pollutants, Chemical) RN - 3417WMA06D (Benzo(a)pyrene) RN - 423D2T571U (Ethinyl Estradiol) RN - 63231-63-0 (RNA) SB - IM MH - Animals MH - Benzo(a)pyrene/*toxicity MH - Cluster Analysis MH - Environmental Exposure/*analysis MH - Ethinyl Estradiol/*toxicity MH - Female MH - Gadus morhua/*genetics/metabolism MH - Gene Expression Profiling MH - Gene Regulatory Networks/drug effects MH - Liver/drug effects/*metabolism MH - Male MH - Molecular Sequence Annotation MH - RNA/metabolism MH - Sequence Analysis, RNA/*methods MH - Tissue Survival/drug effects MH - Transcriptome/*genetics MH - Water Pollutants, Chemical/toxicity OTO - NOTNLM OT - Ahr OT - Atlantic cod OT - Esr1 OT - Liver OT - RNA-Seq EDAT- 2018/06/22 06:00 MHDA- 2018/08/18 06:00 CRDT- 2018/06/22 06:00 PHST- 2017/10/31 00:00 [received] PHST- 2018/06/01 00:00 [revised] PHST- 2018/06/06 00:00 [accepted] PHST- 2018/06/22 06:00 [pubmed] PHST- 2018/08/18 06:00 [medline] PHST- 2018/06/22 06:00 [entrez] AID - S0166-445X(18)30521-6 [pii] AID - 10.1016/j.aquatox.2018.06.003 [doi] PST - ppublish SO - Aquat Toxicol. 2018 Aug;201:174-186. doi: 10.1016/j.aquatox.2018.06.003. Epub 2018 Jun 7.