ABSTRACT: Transcriptomic and behavioural data reveal elevated neurotoxic effects of PCB-153 when co-exposed with polystyrene nanoplastics in zebrafish larvae
Project description:Purpose: to investigate transcriptomal differences between wild-type and SXR/PXR knockout mice and the impact of PCB-153 exposure to both strains to help reveal the mechanism behind the phenotype of hemolytic anemia observed in SXR knockout mice exposed to PCB-153
Project description:In order to investigate the underlying mechanisms of PCB 153 mediated toxicity to Atlantic cod (Gadus morhua), we analyzed the liver proteome of fish exposed to various doses of PCB 153 (0, 0.5, 2 and 8mg/kg body weight) for two weeks and examined the effects on expression of liver proteins using quantitative proteomics. Label-free mass spectrometry enabled quantification of 1272 proteins, and 78 were differentially regulated between PCB 153 treated samples and controls. Two proteins downregulated due to PCB 153 treatment, Glutathione S-transferase theta 1 (GSTT1) and sulfotransferase family protein 1 (ST2B1), were verified using selected reaction monitoring (SRM). Supported by bioinformatics analyses, we concluded that PCB 153 perturbs lipid metabolism in the Atlantic cod liver and that increased levels of lipogenic enzymes indicate increased synthesis of fatty acids and triglycerides.
Project description:Killifish (Fundulus heteroclitus) inhabiting the New Bedford Harbor (NBH) Superfund Site have evolved resistance to the toxic and biochemical effects of non-ortho (dioxin-like) polychlorinated biphenyls (DL-PCBs) and other compounds that act via the aryl hydrocarbon receptor (AHR) signaling pathway. However, the majority of PCBs in NBH are ortho-substituted (non-DL) PCBs (o-PCBs), and the impacts of these o-PCBs on fish populations are not well understood. To determine whether the NBH killifish population has adapted to o-PCBs, we performed a series of experiments involving exposure to killifish embryos and adults from NBH and a reference site (Scorton Creek; SC) to 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB-153), a model o-PCB. PCB-153 was not acutely embryotoxic to developing F2 killifish embryos (SC or NBH) at concentrations up to 28 µM. RNA-seq showed that SC embryos exposed to PCB-153 (28 µM for 6 hr at 10 days post fertilization) had changes in the expression of genes involved in glucose homeostasis. However, NBH embryos were much less sensitive to these effects of PCB-153. When adult killifish from SC and NBH were exposed to PCB-153 (20 mg/kg) and sampled 3 days later for gene expression, many more genes were affected in forebrains of SC fish than in NBH fish, in a sex-specific manner. Together, these results demonstrate that NBH killifish have evolved reduced sensitivity to o-PCBs, suggesting complex adaptation to chemical mixtures at a Superfund site.
Project description:Nanoplastics pollution is a rising environmental concern whose impacts on biodiversity and human health are far from being understood. This is particularly salient in aquatic ecosystems, where the majority of species depend on external fertilization for reproduction. Here we evaluated the effects of a short-term exposure to engineered polystyrene nanoplastics (NPs) in the zebrafish germ line to further explore their impact on reproduction. To this end, zebrafish (Danio rerio) were exposed to 5 mg/L of 45 nm polystyrene (PS)-NPs via water for 96h. We show that, in males, nanoplastics induced testicular histological alterations with abnormal sperm clustering and chromatin compaction, resulting in viable spermatozoa but with reduced motility. Moreover, in females we observed an alteration in oocyte stages frequencies during oogenesis, possibly reflecting alterations in oocyte growth. RNA-sequencing analysis in male testis links nanoplastic induced alterations in the expression of genes involved in chromatin structure, meiosis and DNA double-strand break formation and repair progression, and gametes recognition. Flow cytometry analysis revealed that the observed effects in males were directly due to nanoplastics penetrating the testicular barrier and being internalized within germline cells. Overall, our results demonstrate that acute exposure to NPs can compromise reproductive fitness, underscoring the environmental and health impacts of NPs pollution.
Project description:Nanoplastics are produced by breakdown of plastics in environmental contamination or commercial use for cosmetics or daily expenses. Emerging evidence indicate that ingested nanoplastics with a size smaller than 100 nm have the potential to reach the brain and induces neurotoxicity. However, the potential toxicity of nanoplastics on brain are limited because of difficulties in synthesize of nanoplastics. In present study, we synthesized the fluorescent polystyrene nanoplastics (PSNPs) and examined the toxicity of PSNPs in brain in vivo and in vitro analyses by comparison to IR-813 fluorophore. Synthesized PSNPs were characterized by fluorescence imaging system, scanning electron microscopy, and Fourier-transform infrared spectroscopy. PSNPs were detected in adult mice brain by oral ingestion. In addition, a series of behavioral analyses showed that oral ingestion of PSNPs induced memory impairments. Among brain cells, PSNPs were predominantly internalized in microglia, and uptake of PSNPs induced microglial activation. In addition, the conditioned medium derived from microglia exposed to PSNPs repressed hippocampal neuronal activity. Furthermore, transcriptome analysis showed that PSNPs changed gene expressions in microglia, elevation of neuroinflammation in contrast to suppression of neurotrophic factors. These results indicated that predominant uptake of PSNPs in microglia induced elevation of neuroninflammatory responses whereas suppression of neurotrophic factors that may contribute to the cognitive impairment. Our findings indicate the toxic mechanism and potential detrimental effect of nanoplastic in brain and suggest a potential risk of cognitive impairment by exposure to nanoplastics.
Project description:In this study, we explore the implications of oral exposure to the MARBLES mixture on the brain in adult female mice through two omics approaches, metabolomics and transcriptomics. The individual PCB congeners (PCB 11, 28, 52, 84, 95, 101, 118, 135, 138, 149, 153, and 180) used to make the MARBLES PCB mix. Female C57Bl/6J mice (> 6-week-old) were randomized into exposure groups (N = 4-6) and orally exposed to 0, 0.1, 1, or 6 mg/kg bw/day of the MARBLES mix in organic peanut butter/organic peanut oil for 7 weeks.The striatum and prefrontal cortex were isolated and, together with the liver, prepared for RNA sequencing.
Project description:Genome-wide gene expression assay was used to map the genes affected in the liver of Atlantic cod treated with the persistent environmental pollutant polychlorinated biphenyl 153 (PCB 153) (0.5, 2 and 8 mg/kg body weight).
2014-12-31 | GSE43733 | GEO
Project description:Polystyrene nanoplastics enhance the toxicological effects of DDE in zebrafish larvae
Project description:These experiments were designed to produce the appropriate controls so that their cohort's transcript (mRNA) changes in whole circulating blood could be determined. The cohorts were exposed to D-amphetamine under a neurotoxic and non-neurotoxic condition or subjected to elevated environmental temperatures that produced a hyperthermia very similar to heat stroke. The cohort data is in a separate, but linked, GEO file.
Project description:These experiments were designed to detect transcript (mRNA) changes in whole circulating blood in animals exposed to D-amphetamine under neurotoxic and non-neurotoxic conditions, or subjected to elevated environmental temperatures that produced a hyperthermia very similar to heat stroke. The study objectives were: 1) to detect transcript changes in blood due to life-threatening hyperthermia produced by elevated environmental temperatures (39°C, produces no or minimal neurotoxicity); 2) detect transcripts that could serve as biomarkers specific for neurotoxic amphetamine exposures and not seen with environmentally-induced hyperthermia; and 3) determine the transcript changes related to the immune system in circulating blood produced by either non-neurotoxic or neurotoxic amphetamine exposures. Amphetamine effects on gene expression are dependent on body temperature and indicate that many significant changes in genes related to the immune system occur, some likely in response to damage, even when animals remain normothermic during amphetamine exposure. Also, hyperthermia alone produces many changes in immune related genes in blood