ABSTRACT: Transcriptomic responses to Deepwater Horizon oil in mahi-mahi (Coryphaena hippurus) embryos reveals time and oil-dependent linkages between molecular initiating events and developmental toxicity
Project description:Purpose:To help identify molecular mechanisms and pathways potentially involved in the developmental toxicity for fish exposed to Deepwater Horizon (DWH) oil, transcriptomic profiles in mahi-mahi (Coryphaena hippurus) embryos exposed to different DWH oils (source and artificially weathered oil) were evaluated at different critical windows of development using High Throughput Sequencing (HTS). Methods:Total mRNA profiles of 24, 48, 96 hpf mahi-mahi larvae after slick and source oil exposure were generated by deep sequencing, in triplicate, using Illumina HiSeq2500. qRTâPCR validation was performed using SYBR Green assays. Results: Exposure to slick oil induced more pronounced changes in gene expression over time than did exposure to source oil. Predominant transcriptomic responses included alteration of E1F2 signaling, steroid biosynthesis, ribosome biogenesis, perturbation in eye development and peripheral nervous, and activation of P450 pathway. Comparisons of changes of cardiac / Ca2+-associated genes with phenotypic responses revealed reduced heart rate and increased pericardial edema in larvae exposed to slick oil but not source oil. Total mRNA profiles of 24, 48, 96 hpf mahi-mahi larvae after slick and source (mass) oil exposure were generated by deep sequencing, in triplicate, using Illumina HiSeq2500.
Project description:Purpose: To help identify molecular regulatory mechanisms of developmental toxicity for fish exposed to Deepwater Horizon (DWH) oil, microRNA profiles in mahi-mahi (Coryphaena hippurus) larvae exposed to different DWH oils (source/mass and artificially weathered oil) were evaluated using High Throughput Sequencing (HTS). Methods: Total microRNA profiles of 48 hpf mahi-mah larvae after slick (0.5%, 1%, and 2%) and source/mass oil (0.125%, 0.25% and 5%) exposure were generated by deep sequencing, in triplicate, using Illumina NextSEQ v2. Results: Among over 100 significant DE miRNAs, DE miRNAs that were inversely correlated with target mRNAs after slick and source oil exposure were identfied. miR-34b, miR-181b, miR-23b, and miR-203a responsive to both slick and source oil exposure were further filtered to predict downstream biological functions. The target genes of these four miRNAs were involved AhR signaling, Cardiac β-adrenergic signaling, nNOS signaling in neurons, xenobiotic metabolism signaling, p53 signaling, cell cycle regulation, etc., as well as potential diseases including cardiovascular disease, neurological disease, developmental disorder, ophthalmic disease, metabolism disease, etc.
Project description:Purpose:To help identify molecular mechanisms and pathways potentially involved in the developmental toxicity for fish exposed to Deepwater Horizon (DWH) oil, transcriptomic profiles in mahi-mahi (Coryphaena hippurus) embryos exposed to different DWH oils (source and artificially weathered oil) were evaluated at different critical windows of development using High Throughput Sequencing (HTS). Methods:Total mRNA profiles of 24, 48, 96 hpf mahi-mahi larvae after slick and source oil exposure were generated by deep sequencing, in triplicate, using Illumina HiSeq2500. qRT–PCR validation was performed using SYBR Green assays. Results: Exposure to slick oil induced more pronounced changes in gene expression over time than did exposure to source oil. Predominant transcriptomic responses included alteration of E1F2 signaling, steroid biosynthesis, ribosome biogenesis, perturbation in eye development and peripheral nervous, and activation of P450 pathway. Comparisons of changes of cardiac / Ca2+-associated genes with phenotypic responses revealed reduced heart rate and increased pericardial edema in larvae exposed to slick oil but not source oil.
Project description:Purpose:To help identify the role miRNAs in molecular mechanisms and pathways potentially involved in the developmental toxicity for fish exposed to Deepwater Horizon (DWH) oil, miRNA-mRNA networks in mahi-mahi (Coryphaena hippurus) embryos exposed to different DWH oils (source and artificially weathered oil) were evaluated at different critical windows of development using High Throughput Sequencing (HTS). Methods:miRNA profiles of 24, 48, 96 hpf mahi-mah larvae after slick and source oil exposure were generated by deep sequencing, in triplicate, using Illumina NextSeq v2. qRT–PCR validation was performed using SYBR Green assays. Results: Exposure of embryos to slick oil resulted in more DE miRNAs than source oil at all developmental stages 24hpf, 48hpf, and 96hpf. There was also an increase in the number of DE miRNA as development progressed, with 96hpf having the highest number of DE miRNAs. The expression of miRNAs and their target mRNA was further compared using advanced bioinformatics with subsequent target organ predictions based on their interactions. Gene ontology (GO) analysis on the target mRNAs was consistent with pathway analysis of miRNAs, predicting disruption of cardiovascular system development after oil exposure and showed that specific miRNA–mRNA interactions may contribute to these effects.
Project description:Purpose:To help identify molecular mechanisms and pathways potentially involved in the developmental toxicity for fish exposed to different concentrations of Deepwater Horizon (DWH) oil, transcriptomic profiles in mahi-mahi (Coryphaena hippurus) embryos exposed to different DWH oils (source and artificially weathered oil) were evaluated using High Throughput Sequencing (HTS). Methods:Total mRNA profiles of 48 hpf mahi-mah larvae after slick (0.5%, 1%, and 2%) and source/mass oil (0.125%, 0.25% and 5%) exposure were generated by deep sequencing, in triplicate, using Illumina NextSEQ v2. Results:To determine the potential biological impact of oil exposure at system level, a gene ontology (GO) term analysis on biological processes (BPs) was conducted by analyzing the DEGs using ToppGene. The profile of BPs was dose- and oil type- dependent. After exposure to 0.125% slick oil, the top enriched biological processes were RNA processing and RNA metabolism terms. Metabolic and catabolic process and terms associated with embryo development were some of the most enriched BPs at 0.25% slick oil. The top enriched BPs at 0.5% slick oil were organic acid metabolic process and cardiovascular system development. For source oil, cell cycle process, metabolic process, and RNA processing were the most enriched by 0.125% source oil exposure, which were also highly enriched by 0.25% source oil exposure, while more ‘response’ BPs were enriched by 0.25% source oil exposure, such as regulation of response to stress, response to endogenous stimulus, response to hormone, cellular response to light stimulus, etc. The most significantly enrich BP by 0.5% source oil was cardiovascular system development followed by organic acid metabolic process and cell junction assembly.
