| 1. |
- Keiter, Susanne, et al.
(author)
-
Does perfluorooctane sulfonate (PFOS) act as chemosensitizer in zebrafish embryos?
- 2016
-
In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 548-549, s. 317-324
-
Journal article (peer-reviewed)abstract
- Earlier studies have shown that perfluorooctane sulfonate (PFOS) increases the toxicity of other chemicals by enhancing their uptake by cells and tissues. The present study aimed at testing whether the underlying mechanism of enhanced uptake of chemicals by zebrafish (Danio rerio) embryos in the presence of PFOS is by interference of this compound with the cellular efflux transporter Abcb4. Modifications of uptake/clearance and toxicity of two Abcb4 substrates, the fluorescent dye rhodamine B (RhB) and vinblastine, by PFOS were evaluated using 24 and 48. h post-fertilization (hpf) embryos. Upon 90. min exposure of 24. hpf embryos to 1. μM RhB and different PFOS concentrations (3-300. μM) accumulation of RhB in zebrafish was increased by up to 11.9-fold compared to controls, whereas RhB increases in verapamil treatments were 1.7-fold. Co-administration of PFOS and vinblastine in exposures from 0 to 48. hpf resulted in higher vinblastine-caused mortalities in zebrafish embryos indicating increased uptake of this compound. Interference of PFOS with zebrafish Abcb4 activity was further studied using recombinant protein obtained with the baculovirus expression system. PFOS lead to a concentration-dependent decrease of the verapamil-stimulated Abcb4 ATPase activity; at higher PFOS concentrations (250, 500. μM), also the basal ATPase activity was lowered indicating PFOS to be an Abcb4 inhibitor. In exposures of 48. hpf embryos to a very high RhB concentration (200. μM), accumulation of RhB in embryo tissue and adsorption to the chorion were increased in the presence of 50 or 100. μM PFOS. In conclusion, the results indicate that PFOS acts as inhibitor of zebrafish Abcb4; however, the exceptionally large PFOS-caused effect amplitude of RhB accumulation in the 1. μM RhB experiments and the clear PFOS effects in the experiments with 200. μM RhB suggest that an additional mechanism appears to be responsible for the potential of PFOS to enhance uptake of Abcb4 substrates.
|
|
| 2. |
- Otte, Jens, et al.
(author)
-
Contribution of Priority PAHs and POPs to Ah Receptor-Mediated Activities in Sediment Samples from the RiverElbe Estuary, Germany
- 2013
-
In: PLOS ONE. - San Francisco, USA : Public Library Service. - 1932-6203. ; 8:10
-
Journal article (peer-reviewed)abstract
- The estuary of the River Elbe between Hamburg and the North Sea (Germany) is a sink for contaminated sediment and suspended particulate matter (SPM). One major concern is the effect of human activities on the hydrodynamics, particularlythe intensive dredging activities in this area that may result in remobilization of sediment-bound pollutants. The aim of this study was to identify pollutants contributing to the toxicological risk associated with re-suspension of sediments in the Elbe Estuary by use of an effect-directed analysis that combines chemical and biological analyses in with specific fractionation techniques. Sediments were collected from sites along the Elbe Estuary and a site from a small harbor basin of the Elbe Estuary that is known to be polluted. The sixteen priority EPA-PAHs were quantified in organic extracts of sediments. In addition, dioxin equivalents of sediments were investigated by use of the 7-ethoxyresorufin O-deethylase assay with RTL-W1 cells and the Ah receptor-mediated luciferase transactivation assay with H4IIE-luc cells. Quantification of the 16 priorityPAHs revealed that sediments were moderately contaminated at all of the sites in the Elbe River Estuary (,0.02–0.906 mg/gdw). Sediments contained relatively small concentrations of dioxin equivalents (Bio-TEQ) with concentrations ranging from15.5 to 322 pg/g dw, which were significantly correlated with dioxin equivalents calculated based on toxicity referencevalues and concentrations of PAH. The concentration of Bio-TEQ at the reference site exceeded 200,000 pg/g dw. In apotency balance the 16 PAHs explained between 47 and 118% of the Bio-TEQ in the luciferase assay, which can be explained by the constant input of PAHs bound to SPM from the upper course of the Elbe River into its estuary. Successful identification of a significant portion of dioxin-like activity to priority PAHs in complex environmental samples such assediments has rarely been reported.
|
|
| 3. |
- Alfonso, Sébastien, et al.
(author)
-
Examining multi- and transgenerational behavioral and molecular alterations resulting from parental exposure to an environmental PCB and PBDE mixture
- 2019
-
In: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 208, s. 29-38
-
Journal article (peer-reviewed)abstract
- Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants extensively used during the 20th century and still present in aquatic environments despite their ban. Effects of exposure to these compounds over generations are poorly documented. Therefore, our aims were to characterize behavioral responses and underlying molecular mechanisms in zebrafish exposed to an environmentally relevant mixture of PCBs and PBDEs as well as in four unexposed offspring generations. Zebrafish (F0) were chronically exposed from the first meal onward to a diet spiked with a mixture containing 22 PCB and 7 PBDE congeners in proportions and concentrations reflecting environmental situations (ΣPCBs = 1991 and ΣPBDEs = 411 ng/g). Four offspring generations (F1 to F4) were obtained from this F0 and were not further exposed. Behavior was assessed at both larval and adult stages. Mechanisms related to behavioral defects (habenula maturation and c-fos transcription) and methylation (dnmts transcription) were monitored in larvae. Exposed adult F0 as well as F1 and F3 adults displayed no behavioral change while F2 expressed anxiety-like behavior. Larval behavior was also disrupted, i.e. hyperactive after light to dark transition in F1 or hypoactive in F2, F3 and F4. Behavioral disruptions may be related to defect in habenula maturation (observed in F1) and change in c-fos transcription (observed in F1 and F2). Transcription of the gene encoding DNA methyltransferase (dnmt3ba) was also modified in all generations. Our results lead us to hypothesize that chronic dietary exposure to an environmentally relevant mixture of PCB and PBDE triggers multigenerational and transgenerational molecular and behavioral disruptions in a vertebrate model.
|
|
| 4. |
- Batel, A., et al.
(author)
-
Histological, enzymatic and chemical analyses of the potential effects of differently sized microplastic particles upon long-term ingestion in zebrafish (Danio rerio)
- 2020
-
In: Marine Pollution Bulletin. - : Elsevier. - 0025-326X .- 1879-3363. ; 153
-
Journal article (peer-reviewed)abstract
- In microplastics (MPs) research, there is an urgent need to critically reconsider methodological approaches and results published, since public opinion and political decisions might be based on studies using debatable methods and reporting questionable results. For instance, recent studies claim that MPs induce intestinal damage and that relatively large MPs are transferred to, e.g., livers in fish. However, there is methodological criticism and considerable concern whether MP transfer to surrounding tissues is plausible. Likewise, there is an ongoing discussion in MP research if MPs act as vectors for adsorbed hazardous chemicals. In this study, effects of very small (4–6 μm) and very large (125–500 μm) benzo(a) pyrene (BaP)-spiked polyethylene (PE) particles administered via different uptake routes (food chain vs. direct uptake) were compared in a 21-day zebrafish (Danio rerio) feeding experiment. Particular care was taken to prevent cross-contamination of MPs during dissection and histological sample preparation. In contrast to numerous reports in literature describing similar approaches, independent of exposure route and MP size, no adverse effects could be detected. Likewise, no BaP accumulation could be documented, and MPs were exclusively seen in the lumen of the intestinal tract, which, however, did not induce any histopathological effects. Results indicate that in fish MPs are taken up, pass along the intestinal lumen and are excreted without any symptoms of adverse effects.
|
|
| 5. |
- Beiras, R., et al.
(author)
-
Ingestion and contact with polyethylene microplastics does not cause acute toxicity on marine zooplankton
- 2018
-
In: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 360, s. 452-460
-
Journal article (peer-reviewed)abstract
- Toxicity of polyethylene microplastics (PE-MP) of size ranges similar to their natural food to zooplanktonic organisms representative of the main taxa present in marine plankton, including rotifers, copepods, bivalves, echinoderms and fish, was evaluated. Early life stages (ELS) were prioritized as testing models in order to maximize sensitivity. Treatments included particles spiked with benzophenone-3 (BP-3), a hydrophobic organic chemical used in cosmetics with direct input in coastal areas. Despite documented ingestion of both virgin and BP-3 spiked microplastics no acute toxicity was found at loads orders of magnitude above environmentally relevant concentrations on any of the invertebrate models. In fish tests some effects, including premature or reduced hatching, were observed after 12 d exposure at 10 mg L-1 of BP-3 spiked PE-MP. The results obtained do not support environmentally relevant risk of microplastics on marine zooplankton. Similar approaches testing more hydrophobic chemicals with higher acute toxicity are needed before these conclusions could be extended to other organic pollutants common in marine ecosystems. Therefore, the replacement of these polymers in consumer products must be carefully considered.
|
|
| 6. |
|
|
| 7. |
- Blanc, Mélanie, 1993-, et al.
(author)
-
An environmentally relevant mixture of polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) disrupts mitochondrial function, lipid metabolism and neurotransmission in the brain of exposed zebrafish and their unexposed F2 offspring
- 2021
-
In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 754
-
Journal article (peer-reviewed)abstract
- Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants still present in aquatic environments despite their total or partial ban. Previously, we observed that an environmentally realistic mixture of these compounds affects energy balance, growth, and reproduction in exposed zebrafish (F0), and behavior in their unexposed offspring (F1-F4). In the present work, we performed lipidomic and transcriptomic analyses on brains of zebrafish (F0-F2) from exposed and control lineages to identify molecular changes that could explain the observed phenotypes. The use of both technologies highlighted that F0 zebrafish displayed impaired mitochondrial function and lipid metabolism regulation (depletion in triacylglycerols and phospholipids) which can explain disruption of energy homeostasis. A subset of the regulated biological pathways related to energetic metabolism and neurotransmission were inherited in 12. In addition, there were increasing effects on epigenetic pathways from the F0 to the F2 generation. Altogether, we show that the effects of an environmental exposure to PCBs and PBDEs on energetic metabolism as well as neurotransmission extend over 2 generations of zebrafish, possibly due to transgenerational epigenetic inheritance.
|
|
| 8. |
- Blanc, Mélanie, 1993-, et al.
(author)
-
Environmental chemicals differentially affect epigenetic-related mechanisms in the zebrafish liver (ZF-L) cell line and in zebrafish embryos
- 2019
-
In: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 215
-
Journal article (peer-reviewed)abstract
- A number of chemicals have been shown to affect epigenetic patterning and functions. Since epigenetic mechanisms regulate transcriptional networks, epigenetic changes induced by chemical exposure can represent early molecular events for long-term adverse physiological effects. Epigenetics has thus appeared as a research field of major interest within (eco)toxicological sciences. The present study aimed at measuring effects on epigenetic-related mechanisms of selected environmental chemicals (bisphenols, perfluorinated chemicals, methoxychlor, permethrin, vinclozolin and coumarin 47) in zebrafish embryos and liver cells (ZFL). Transcription of genes related to DNA methylation and histone modifications was measured and global DNA methylation was assessed in ZFL cells using the LUMA assay. The differences in results gathered from both models suggest that chemicals affect different mechanisms related to epigenetics in embryos and cells. In zebrafish embryos, exposure to bisphenol A, coumarin 47, methoxychlor and permethrin lead to significant transcriptional changes in epigenetic factors suggesting that they can impact early epigenome reprogramming related to embryonic development. In ZFL cells, significant transcriptional changes were observed upon exposure to all chemicals but coumarin 47; however, only perfluorooctane sulfonate induced significant effects on global DNA methylation. Notably, in contrast to the other tested chemicals, perfluorooctane sulfonate affected only the expression of the histone demethylase kdm5ba. In addition, kdm5ba appeared as a sensitive gene in zebrafish embryos as well. Taken together, the present results suggest a role for kdm5ba in regulating epigenetic patterns in response to chemical exposure, even though mechanisms remain unclear. To confirm these findings, further evidence is required regarding changes in site-specific histone marks and DNA methylation together with their long-term effects on physiological outcomes.
|
|
| 9. |
- Blanc, Mélanie, 1993-
(author)
-
How can an organism´s life experience affect their descendants? Insights from epigenetic and transgenerational effects of chemical exposure in zebrafish
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- Environmental pollution causes approx. 10% of human diseases, and some develop in the progeny because of parental exposure. Effects passed on to subsequent generations may be a consequence of genetic mutations, or of inherited changes in epigenetic patterns. Epigenetics is the study of mitotically or meiotically heritable changes in gene function that cannot be explained by changes in the DNA sequence. Several chemicals have been suggested to induce epigenetic dysregulation leading to multigenerational and transgenerational effects, i.e. effects that can be observed in completely unexposed generations. However, mechanisms underlying the inheritance of epigenetic changes and their implication in phenotypic adversities are complex and not well-understood. The overall aim of this thesis was to study adverse effects and underlying molecular changes in several generations of zebrafish after parental exposure to selected industrial chemicals. To this end, molecular (lipidomic, transcriptomic, epigenomic) and behavioral analyses were performed. Zebrafish is an acknowledged model for vertebrates in toxicology and biomedicine; as such, the findings can be relevant to many organisms including human. The results from this thesis showed that different types of chemicals, polychlorinated biphenyls, polybromodiphenyl ethers, and permethrin, induced transgenerational effects in concentrations relevant to environmental or human exposures. Impact on anxiety and locomotor activity of zebrafish was observed over several generations. Gene expression and epigenetic (DNA methylation) alterations were partly inherited and suggest stable alteration of specific functions such as glutamatergic/GABAergic neurotransmission and synaptic plasticity. Finally, the findings shed light on experimental limitations and research perspectives, which we expect will contribute to the design of future studies on epigenetically inherited effects of any environmental stress.
|
|
| 10. |
- Blanc, Mélanie, 1993-, et al.
(author)
-
Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126)
- 2017
-
In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 590-591, s. 249-257
-
Journal article (peer-reviewed)abstract
- Perfluorooctane sulfonic acid (PFOS) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways. For this purpose, zebrafish embryos were exposed in semi-static conditions to 7.5 μg/L of PCB126 alone, in the presence of 25 mg/L of PFOS, 15.7 mg/L of PFHxA or in the presence of both PFOS and PFHxA. Quantitative PCR was performed on embryos aged from 24 h post fertilization (hpf) to 96 hpf to investigate expression changes of genes involved in metabolism of xenobiotics (ahr2, cyp1a), oxidative stress (gpx1a, tp53), lipids metabolism (acaa2, osbpl1a), and epigenetic mechanisms (dnmt1, dnmt3ba). Cyp1a and ahr2 expression were significantly induced by the presence of PCB126. However, after 72 and 78 h of exposure, induction of cyp1a expression was significantly lower when embryos were co-exposed to PCB126 + PFOS + PFHxA when compared to PCB126-exposed embryos. Significant upregulation of gpx1a occurred after exposure to PCB126 + PFHxA and to PCB126 + PFOS + PFHxA at 30 and 48 hpf. Besides, embryos appeared more sensitive to PCB126 + PFOS + PFHxA at 78 hpf: acaa2 and osbpl1a were significantly downregulated; dnmt1 was significantly upregulated. While presented as environmentally safe, PFHxA demonstrated that it could affect gene expression patterns in zebrafish embryos when combined to PFOS and PCB126, suggesting that such mixture may increase PCB126 toxicity. This is of particular relevance since PFHxA is persistent and still being ejected into the environment. Moreover, it provides additional information as to the importance to integrate mixture effects of chemicals in risk assessment and biomonitoring frameworks.
|
|
