Dataset Information

Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish

ABSTRACT: Polychlorinated biphenyls (PCBs) persist in the environment as complex mixtures and undergo extensive biotransformation, yet the developmental toxicity of PCB metabolites remains poorly defined. We evaluated developmental, neurobehavioral, and molecular effects of parent PCBs, hydroxylated, methoxylated, and sulfated metabolites, and environmentally relevant mixtures using embryonic zebrafish. Morphological abnormalities and photomotor behavior were assessed across early development, followed by targeted cyp1a reporter analysis and transcriptomic profiling for a subset of potent exposures. Most chemicals induced morphological effects, with hydroxylated and sulfated metabolites producing effects more frequently and at lower benchmark concentrations than parent congeners. Behavioral alterations were more prevalent in embryonic photomotor response than larval photomotor response and generally co-occurred with morphological effects. Environmental mixtures elicited broad phenotypic profiles comparable to highly active individual compounds. Despite pronounced developmental toxicity, cyp1a induction was limited to PCB126, indicating that aryl hydrocarbon receptor activation was not a dominant mechanism for most exposures. Transcriptomic analyses revealed minimal responses for parent PCBs but robust, exposure-specific gene expression changes for select metabolites, particularly 5-OH-PCB11, and mixtures. Differentially expressed genes were enriched for xenobiotic metabolism, immune signaling, and neuroactive pathways, alongside consistent downregulation of circadian regulators. Together these results demonstrate contributions of PCB metabolites and mixtures to toxicity.

ORGANISM(S): Danio rerio

PROVIDER: GSE326509 | GEO | 2026/03/31

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Hydroxylated polychlorinated biphenyls are the metabolites produced from polychlorinated biphenyls (PCBs) by drug-metabolizing enzyme cytochrome P450 1A1. These compounds are bound to transthyretin, a major plasma thyroid hormone-binding protein in amphibian tadpoles. The compounds-transthyretin complexes are transferred into the brain across the blood brain barrier in mammals. Thus these compounds are suspected to disrupt neural development in brain. We studied about the effects of hydroxylated PCBs on the thyroid system in brain using metamorphosing tadpoles of African clawed toad, Xenopus laevis. The metamorphosis assay revealed that these compounds had inhibitory effects on the thyroid hormone-induced metamorphosis. This in vivo assay was a powerful tool to detect thyroid-disrupting activities, because we were not able to detect the inhibitory effects of these compounds using thyroid hormone-responsive reporter gene assay in a cultured Xenopus cell line. A genome-wide gene expression analysis in brain following short-term exposure to these compounds demonstrated that the delay of metamorphosis and the morphological thyroid-disrupting changes could be caused partially by disruption of the thyroid hormone-induced gene expression by hydroxylated PCBs. Furthermore, we associated functional ontology terms with the transcripts whose expression were altered by thyroid hormone alone, or thyroid hormone and hydroxylated PCBs. We suggested that these approachs using a technique of bioinformatics revealed molecular mechanism of thyroid-disrupting activities in vivo. Thyroid hormones induce amphibian metamorphosis and alter a lot of thyroid hormone-responsive gene expression. We studied about the effects of hydroxylated PCBs on TH-induced gene expression. Premetamorphic tadpoles were treated with 500 nM hydroxylated PCBs in the presence of 1 nM thyroid hormone for 4 days. After exposure period total RNA was extracted from brain. Study included at least three replicate of each treatment.

Project description:We analyzed the transcriptional response of the actinomycete Rhodococcus aetherivorans I24 to biphenyl and polychlorinated biphenyls (PCBs). This species has not been extensively exposed to PCBs, as it was first isolated from a toluene contaminated aquifer, rather than a site contaminated with polychlorinated hydrocarbons. Using a microarray targeting 3524 genes, we assessed gene expression in minimal medium supplemented with various substrates (e.g. PCBs) and in both PCB-contaminated and non-contaminated sediment slurries. Relative to the reference condition (minimal medium supplemented with glucose), 408 genes were up-regulated in the various treatments. In medium and in sediment, PCBs elicited the up-regulation of a common set of 100 genes, including chaperones (groEL), a superoxide dismutase (sodA), alkyl hydroperoxide reductase protein C (ahpC), and a catalase/peroxidase (katG). Analysis of the R. aetherivorans I24 genome sequence identified orthologs of many of the genes in the canonical biphenyl pathway, but very few of these genes were up-regulated in response to PCBs or biphenyl. This study is one of the first which utilizes microarrays to assess the transcriptional response of a soil bacterium to a pollutant under conditions which more closely resemble the natural environment. Our results indicate that the transcriptional response of R. aetherivorans I24 to PCBs, in both medium and sediment, is primarily directed towards reducing oxidative stress, rather than catabolism. In addition, the identification of numerous genes expressed in contaminated soil specifically may have implications for the development of biosensors. Finally, comparative genomic and transcriptomic analyses suggest that the mere presence of orthologs of the required enzymes may not be sufficient to confer a vigorous biphenyl/PCB metabolism. RNA was isolated from cells incubated in the following: sediment from a PCB-contaminated industrial site, uncontaminated sediment from a comparable site, and defined media supplemented with glucose (3 g/L), glucose and biphenyl (3 g/L, 4.5 Î¼M), or glucose and PCBs (3 g/L, 5 mg/L Aroclor 1254). In all cases, there were 3 biological replicates and 2 technical replicates (repeat hybridizations). A total of 3524 genes are represented on the arrays; of these, 41 and 176 are found on the plasmids pRA2 and pRA3, respectively. On average, there are 3 distinct 24nt probes per gene.

Dataset Information

Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets