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Alfonso, S., Blanc, M., Joassard, L., Keiter, S. H., Munschy, C., Loizeau, V., et al. (2019). Examining multi- and transgenerational behavioral and molecular alterations resulting from parental exposure to an environmental PCB and PBDE mixture. Aquat. Toxicol., 208, 29–38.
Résumé: 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 (Sigma PCBs = 1991 and Sigma PBDEs = 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, Le. 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.
Mots-Clés: adult zebrafish; Behavior; brominated flame retardants; developmental exposure; dietary-exposure; embryonic exposure; Epigenetic; Gene transcription; global dna methylation; left-right asymmetry; Offspring; Parental exposure; polybrominated diphenyl ethers; polychlorinated-biphenyls pcbs; Zebrafish; zebrafish danio-rerio
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Anastasiadi, D., Vandeputte, M., Sánchez-Baizán, N., Allal, F., & Piferrer, F. (2018). Dynamic epimarks in sex-related genes predict gonad phenotype in the European sea bass, a fish with mixed genetic and environmental sex determination. Epigenetics, 13(9), 988–1011.
Résumé: The integration of genomic and environmental influences into methylation patterns to bring about a phenotype is of central interest in developmental epigenetics, but many details are still unclear. The sex ratios of the species used here, the European sea bass, are determined by genetic and temperature influences. We created four families from parents known to produce offspring with different sex ratios, exposed larvae to masculinizing temperatures and examined, in juvenile gonads, the DNA methylation of seven genes related to sexual development by a targeted sequencing approach. The genes most affected by both genetics and environment were cyp19a1a and dmrt1, with contrasting sex-specific methylation and temperature responses. The relationship between cyp19a1a methylation and expression is relevant to the epigenetic regulation of vertebrate sex, and we report the evidence of such relationship only below a methylation threshold, 80%, and that it was sex-specific: negatively correlated in females but positively correlated in males. From parents to offspring, the methylation in gonads was midway between oocytes and sperm, with bias towards oocytes for amh-r2, er-β2, fsh-r and cyp19a1a. In contrast, dmrt1 levels resembled those of sperm. The methylation of individual CpGs from foxl2, er-β2 and nr3c1 were conserved from parents to offspring, whereas those of cyp19a1a, dmrt1 and amh-r2 were affected by temperature. Utilizing a machine-learning procedure based on the methylation levels of a selected set of CpGs, we present the first, to our knowledge, system based on epigenetic marks capable of predicting sex in an animal with 90% accuracy and discuss possible applications.
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Blanc, M., Cormier, B., Hyotylainen, T., Krauss, M., Scherbak, N., Cousin, X., et al. (2020). Multi- and transgenerational effects following early-life exposure of zebrafish to permethrin and coumarin 47: Impact on growth, fertility, behavior and lipid metabolism. Ecotox. Environ. Safe., 205, 111348.
Résumé: 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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Jueterbock, A., Bostrom, C., Coyer, J. A., Olsen, J. L., Kopp, M., Dhanasiri, A. K. S., et al. (2020). The Seagrass Methylome Is Associated With Variation in Photosynthetic Performance Among Clonal Shoots. Front. Plant Sci., 11, 571646.
Résumé: Evolutionary theory predicts that clonal organisms are more susceptible to extinction than sexually reproducing organisms, due to low genetic variation and slow rates of evolution. In agreement, conservation management considers genetic variation as the ultimate measure of a population's ability to survive over time. However, clonal plants are among the oldest living organisms on our planet. Here, we test the hypothesis that clonal seagrass meadows display epigenetic variation that complements genetic variation as a source of phenotypic variation. In a clonal meadow of the seagrassZostera marina, we characterized DNA methylation among 42 shoots. We also sequenced the whole genome of 10 shoots to correlate methylation patterns with photosynthetic performance under exposure to and recovery from 27 degrees C, while controlling for somatic mutations. Here, we show for the first time that clonal seagrass shoots display DNA methylation variation that is independent from underlying genetic variation, and associated with variation in photosynthetic performance under experimental conditions. It remains unknown to what degree this association could be influenced by epigenetic responses to transplantation-related stress, given that the methylomes showed a strong shift under acclimation to laboratory conditions. The lack of untreated control samples in the heat stress experiment did not allow us to distinguish methylome shifts induced by acclimation from such induced by heat stress. Notwithstanding, the co-variation in DNA methylation and photosynthetic performance may be linkedviagene expression because methylation patterns varied in functionally relevant genes involved in photosynthesis, and in the repair and prevention of heat-induced protein damage. While genotypic diversity has been shown to enhance stress resilience in seagrass meadows, we suggest that epigenetic variation plays a similar role in meadows dominated by a single genotype. Consequently, conservation management of clonal plants should consider epigenetic variation as indicator of resilience and stability.
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