| 1. |
- Alfonso, Sébastien, et al.
(författare)
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Examining multi- and transgenerational behavioral and molecular alterations resulting from parental exposure to an environmental PCB and PBDE mixture
- 2019
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Ingår i: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 208, s. 29-38
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
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| 3. |
- Blanc, Mélanie, 1993-, et al.
(författare)
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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
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 754
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Tidskriftsartikel (refereegranskat)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.
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| 4. |
- Blanc, Mélanie, 1993-
(författare)
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How can an organism´s life experience affect their descendants? Insights from epigenetic and transgenerational effects of chemical exposure in zebrafish
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 5. |
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| 6. |
- Blanc, Mélanie, 1993-, et al.
(författare)
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Multi- and transgenerational effects following early-life exposure of zebrafish to permethrin and coumarin 47 : Impact on growth, fertility, behavior and lipid metabolism
- 2020
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Ingår i: Ecotoxicology and Environmental Safety. - : Academic Press. - 0147-6513 .- 1090-2414. ; 205
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Tidskriftsartikel (refereegranskat)abstract
- Transgenerational effects induced by environmental stressors are a threat to ecosystems and human health. However, there is still limited observation and understanding of the potential of chemicals to influence life outcomes over several generations. In the present study, we investigated the effects of two environmental contaminants, coumarin 47 and permethrin, on exposed zebrafish (FO) and their progeny (F1-F3). Coumarin 47 is commonly found in personal care products and dyes, whereas permethrin is used as a domestic and agricultural pyrethroid insecticide/insect repellent. Zebrafish (F0) were exposed during early development until 28 days post-fertilization and their progeny (F1-F3) were bred unexposed. On one hand, the effects induced by coumarin 47 suggest no multigenerational toxicity. On the other hand, we found that behavior of zebrafish larvae was significantly affected by exposure to permethrin in F1 to F3 generations with some differences depending on the concentration. This suggests persistent alteration of the neural or neuromuscular function. In addition, lipidomic analyses showed that permethrin treatment was partially correlated with lysophosphatidylcholine levels in zebrafish, an important lipid for neurodevelopment. Overall, these results stress out one of the most widely used pyrethroids can trigger long-term, multi- and possibly transgenerational changes in the nervous system of zebrafish. These neurobehavioral changes echo the effects observed under direct exposure to high concentrations of permethrin and therefore call for more research on mechanisms underlying effect inheritance.
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| 7. |
- Blanc, Mélanie, 1993-, et al.
(författare)
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The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio)
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 779
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Tidskriftsartikel (refereegranskat)abstract
- The pyrethroid insecticide permethrin is widely used for agricultural and domestic purposes. Previous data indicated that it acts as a developmental neurotoxicant and can induce transgenerational effects in non-target organisms. However, associated underlying mechanisms remain unclear. The aim of this study was to investigate permethrin-related transgenerational effects in the zebrafish model, and to identify possible molecular mechanisms underlying inheritance. Zebrafish (F0) were exposed to permethrin during early-life (2 h post-fertilization up to 28 days). The F1 and F2 offspring generations were obtained by pairing exposed F0 males and females, and were bred unexposed. Locomotor and anxiety behavior were investigated, together with transcriptomic and epigenomic (DNA methylation) changes in brains. Permethrin exposed F0 fish were hypoactive at adulthood, while males from the F1 and F2 generations showed a specific decrease in anxiety-like behavior. In F0, transcriptomic data showed enrichment in pathways related to glutamatergic synapse activity, which may partly underlie the behavioral effects. In F1 and F2 males, dysregulation of similar pathways was observed, including a subset of differentially methylated regions that were inherited from the F0 to the F2 generation and indicated stable dysregulation of glutamatergic signaling. Altogether, the present results provide novel evidence on the transgenerational neurotoxic effects of permethrin, as well as mechanistic insight: a transient exposure induces persistent transcriptional and DNA methylation changes that may translate into transgenerational alteration of glutamatergic signaling and, thus, into behavioral alterations.
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| 9. |
- Cormier, Bettie, 1993-, et al.
(författare)
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Chemicals sorbed to environmental microplastics are toxic to early life stages of aquatic organisms
- 2021
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Ingår i: Ecotoxicology and Environmental Safety. - : Academic Press. - 0147-6513 .- 1090-2414. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- Microplastics are ubiquitous in aquatic ecosystems, but little information is currently available on the dangers and risks to living organisms. In order to assess the ecotoxicity of environmental microplastics (MPs), samples were collected from the beaches of two islands in the Guadeloupe archipelago, Petit-Bourg (PB) located on the main island of Guadeloupe and Marie-Galante (MG) on the second island of the archipelago. These samples have a similar polymer composition with mainly polyethylene (PE) and polypropylene (PP). However, these two samples are very dissimilar with regard to their contamination profile and their toxicity. MPs from MG contain more lead, cadmium and organochlorine compounds while those from PB have higher levels of copper, zinc and hydrocarbons. The leachates of these two samples of MPs induced sublethal effects on the growth of sea urchins and on the pulsation frequency of jellyfish ephyrae but not on the development of zebrafish embryos. The toxic effects are much more marked for samples from the PB site than those from the MG site. This work demonstrates that MPs can contain high levels of potentially bioavailable toxic substances that may represent a significant ecotoxicological risk, particularly for the early life stages of aquatic animals.
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| 10. |
- Cormier, Bettie, 1993-, et al.
(författare)
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Chronic feeding exposure to virgin and spiked microplastics disrupts essential biological functions in teleost fish
- 2021
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 415
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Tidskriftsartikel (refereegranskat)abstract
- Toxicity of polyethylene (PE) and polyvinyl chloride (PVC) microplastics (MPs), either virgin or spiked with chemicals, was evaluated in two short-lived fish using a freshwater species, zebrafish, and a marine species, marine medaka. Exposures were performed through diet using environmentally relevant concentrations of MPs over 4 months. No modification of classical biomarkers, lipid peroxidation, genotoxicity or F0 behaviour was observed. A significant decrease in growth was reported after at least two months of exposure. This decrease was similar between species, independent from the type of MPs polymer and the presence or not of spiked chemicals, but was much stronger in females. The reproduction was evaluated and it revealed a significant decrease in the reproductive output for both species and in far more serious numbers in medaka. PVC appeared more reprotoxic than PE as were MPs spiked with PFOS and benzophenone-3 compared to MPs spiked with benzo[a]pyrene. Further, PVC-benzophenone-3 produced behavioural disruption in offspring larvae. These results obtained with two species representing different aquatic environments suggest that microplastics exert toxic effects, slightly different according to polymers and the presence or not of sorbed chemicals, which may lead in all cases to serious ecological disruptions.
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