Suchergebnisse

Exposure to the antifouling tributyltin (TBT) has been related to imposex in mollusks and to obesogenicity, adipogenesis and masculinization in fish. To understand the underlying molecular mechanisms, we evaluated dose-response effects of TBT (1.7-56 nM) in zebrafish eleutheroembryos transcriptome exposed from 2 to 5 days post-fertilization. RNA-sequencing analysis identified 3238 differentially expressed transcripts in eleutheroembryos exposed to TBT. Benchmark dose analyses (BMD) showed that the point of departure (PoD) for transcriptomic effects (9.28 nM) was similar to the metabolomic PoD (11.5 nM) and about one order of magnitude lower than the morphometric PoD (67.9 nM) or the median lethal concentration (LC50: 93.6 nM). Functional analysis of BMD transcriptomic data identified steroid metabolism and cholesterol and vitamin D3 biosynthesis as the most sensitive pathways to TBT (<50% PoD). Conversely, transcripts related to general stress and DNA damage became affected only at doses above the PoD. Therefore, our results indicate that transcriptomes can act as early molecular indicators of pollutant exposure, and illustrates their usefulness for the mechanistic identification of the initial toxic events. As the estimated molecular PoDs are close to environmental levels, we concluded that TBT may represent a substantial risk in some natural environments. ; This work was supported by the European Research Council under the European Union's Seventh Framework Programme (FP/ 2007-2013)/ERC Grant Agreement n. 320737. Some part of this study was also supported by a grant from the Spanish Ministry of Economy and Competitiveness (CTQ2014-56777-R). AEC acknowledges the funding from ISCIII (Spanish Ministry of Economy and Competitiveness, grant number PT17/0009/0019), co-financed by the European Fund for Regional Development (FEDER). RM was supported by a FPU predoctoral fellow from the Spanish Ministry of Education, Culture and Sport (ref. FPU15/03332). ; Peer reviewed

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and involve diverse chemical-receptor interactions that can perturb hormone signaling. The Organization for Economic Co-operation and Development has validated several EDC-receptor bioassays to detect endocrine active chemicals and has established guidelines for regulatory testing of EDCs. Focus on testing over the past decade has been initially directed to EATS modalities (estrogen, androgen, thyroid, and steroidogenesis) and validated tests for chemicals that exert effects through non-EATS modalities are less established. Due to recognition that EDCs are vast in their mechanisms of action, novel bioassays are needed to capture the full scope of activity. Here, we highlight the need for validated assays that detect non-EATS modalities and discuss major international efforts underway to develop such tools for regulatory purposes, focusing on non-EATS modalities of high concern (i.e., retinoic acid, aryl hydrocarbon receptor, peroxisome proliferator-activated receptor, and glucocorticoid signaling). Two case studies are presented with strong evidence amongst animals and human studies for non-EATS disruption and associations with wildlife and human disease. This includes metabolic syndrome and insulin signaling (case study 1) and chemicals that impact the cardiovascular system (case study 2). This is relevant as obesity and cardiovascular disease represent two of the most significant health-related crises of our time. Lastly, emerging topics related to EDCs are discussed, including recognition of crosstalk between the EATS and non-EATS axis, complex mixtures containing a variety of EDCs, adverse outcome pathways for chemicals acting through non-EATS mechanisms, and novel models for testing chemicals. Recommendations and considerations for evaluating non-EATS modalities are proposed. Moving forward, improved understanding of the non-EATS modalities will lead to integrated testing strategies that can be used in regulatory bodies to protect environmental, animal, and human health from harmful environmental chemicals. ; LNM was supported by a H2020-Marie Skłodowska-Curie Action MSCA-IF-RI- 2017 awarded by the European Commission (ref. 797725-EpiSTOX). JK was funded by the European Union's Horizon 2020 research and innovation program under grant agreement GOLIATH No. 825489. AS and LEC were supported by a Grant-in-Aid from the Heart and Stroke Foundation of Canada. ; Peer reviewed

Exposure to PFOS (perfluorooctanesulfonate) has been related to toxic effects on lipid metabolism, immunological response, and different endocrine systems. We present here a transcriptomic analysis of zebrafish embryos exposed to different concentrations of PFOS (0.03–1.0 mg/L) from 48 to 120 hpf. No major survival or morphological alterations (swimming bladder inflation, kyphosis, eye separation and size…) were observed below the 1.0 mg/L mark. Conversely, we observed significant increase in transcripts related to lipid transport and metabolism even at the lowest used concentration. In addition, we observed a general decrease on transcripts related to natural immunity and defense again infections, which adds to the recent concerns about PFOS as immunotoxicant, particularly in humans. Derived PoD (Point of Departure) values for transcriptional changes (0.011 mg/L) were about 200-fold lower than the corresponding PoD values for morphometric effects (2.53 mg/L), and close to levels observed in human blood serum or bird eggs. Our data suggest that currently applicable tolerable levels of PFOS in commercial goods should be re-evaluated, taking into account its potential effects on lipid metabolism and the immune system. ; This work was supported by European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 320737, and by the Spanish Ministry of Economy and Competitiveness (CTM2014-51985-R). AEC acknowledges the funding from ISCIII (Spanish Ministry of Economy and Competitiveness, grant number PT17/0009/0019), co-financed by the European Fund for Regional Development (FEDER). LNM was supported by a Beatriu de Pinos Postdoctoral Fellowship (2013BP-B-00088) funded by the Secretary for Universities and Research of the Department of Economy and Knowledge of the Government of Catalonia and the Cofund programme of the Marie Curie Actions of the 7th R&D Framework Programme of the European Union. RML was supported by an FPU Fellowship (FPU15/03332) from the Spanish Ministry of Education, Culture and Sport. ; Peer reviewed

Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disruptor, its toxicity mechanisms are still poorly understood. We present here a study of its effects on the zebrafish eleutheroembryo transcriptome at concentrations ranging from 0.1 to 4 mg L−1, this latter representing the lowest observed effect concentration (LOEC) found in our study at three different macroscopical endpoints (survival, hatching and swim bladder inflation). Multivariate data analysis methods identified both monotonic and bi-phasic patterns of dose-dependent responses. Functional analyses of genes affected by BPA exposure suggest an interaction of BPA with different signaling pathways, being the estrogenic and retinoid receptors two likely targets. In addition, we identified an apparently unrelated inhibitory effect on, among others, visual function genes. We interpret our data as the result of a sum of underlying, independent molecular mechanisms occurring simultaneously at the exposed animals, well below the macroscopic LOEC, but related to at least some of the observed morphological alterations, particularly in eye size and yolk sac resorption. Our data supports the idea that the physiological effects of BPA cannot be only explained by its rather weak interaction with the estrogen receptor, and that multivariate analyses are required to analyze the effects of toxicants like BPA, which interact with different cellular targets producing complex phenotypes. Estrogenic- and retinoid-like transcriptomic effects of bisphenol A in zebrafish eleutheroembryos and their relationship with morphological alterations. © 2018 Elsevier Ltd ; This work was supported by the European Research Council under the European Union's Seventh Framework Programme ( FP/2007–2013 )/ERC Grant Agreement n. 320737 . Some part of this study was also supported by a grant from the Spanish Ministry of Economy and Competitiveness ( CTQ2014-56777-R ) and by a grant ( PT17/0009/0019 ) from ISCIII (Carlos III Health Institute), part of the Spanish Ministry of Economy and Competitiveness, and cofinanced by the European Regional Development Fund (ERDF). LNM was supported by a Beatriu de Pinos Postdoctoral Fellow ( 2013BP-B-00088 ) awarded by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the Cofund programme of the Marie Curie Actions of the 7th R&D Framework Programme of the European Union. RM was supported by a FPU predoctoral fellow from the Spanish Ministry of Education, Culture and Sport (ref. FPU15/03332 ). We would like to thank Ms. Elia Martinez-Prats and David Angelats for helping with the real time qRT-PCRs measurements. Appendix A ; Peer reviewed

The potential spreading of antibiotic resistance genes (ARG) into agricultural fields and crops represent a fundamental limitation on the use of organic fertilization in food production systems. We present here a study of the effect of spreading four types of organic soil amendments (raw pig slurry, liquid and solid fractions, and a digested derivative) on demonstrative plots in two consecutive productive cycles of corn harvest (Zea mays), using a mineral fertilizer as a control, following the application of organic amendments at 32-62 T per ha (150 kg total N/ha) and allowing 5-8 months between fertilization and harvest. A combination of qPCR and high-throughput 16S rDNA sequencing methods showed a small, but significant impact of the fertilizers in both ARG loads and microbiomes in soil samples, particularly after the second harvesting cycle. The slurry solid fraction showed the largest impact on both ARG loads and microbiome variation, whereas its digestion derivatives showed a much smaller impact. Soil samples with the highest ARG loads also presented increased levels of tetracyclines, indicating a potential dual hazard by ARG and antibiotic residues linked to some organic amendments. Unlike soils, no accumulation of ARG or antibiotics was observed in corn leaves (used as fodder) or grains, and no grain sample reached detection limits for neither parameter. These results support the use of organic soil amendments in corn crops, while proposing the reduction of the loads of ARGs and antibiotics from the fertilizers to greatly reduce their potential risk. ; This work was supported by grants from the LIFE Program of the European Union (LIFE17 ENV/ES/000439), the Spanish Ministry of Science, Innovation and University (MCIN/AEI/10.13039/501100011033, grant RTI2018-096175-B-I00), and the Generalitat de Catalunya (2017SGR902). CSL was supported by a FI predoctoral fellowship from the Generalitat de Catalunya and the European Social Fund (2018 FI B 00368, ESF Investing in your future). IDAEA-CSIC is a Center of ...

Endocrine disrupting chemicals (EDCs) are found in every environmental medium and are chemically diverse. Their presence in water resources can negatively impact the health of both human and wildlife. Currently, there are no mandatory screening mandates or regulations for EDC levels in complex water samples globally. Bioassays, which allow quantifying in vivo or in vitro biological effects of chemicals are used commonly to assess acute toxicity in water. The existing OECD framework to identify single-compound EDCs offers a set of bioassays that are validated for the Estrogen-, Androgen-, and Thyroid hormones, and for Steroidogenesis pathways (EATS). In this review, we discussed bioassays that could be potentially used to screen EDCs in water resources, including in vivo and in vitro bioassays using invertebrates, fish, amphibians, and/or mammalians species. Strengths and weaknesses of samples preparation for complex water samples are discussed. We also review how to calculate the Effect-Based Trigger values, which could serve as thresholds to determine if a given water sample poses a risk based on existing quality standards. This work aims to assist governments and regulatory agencies in developing a testing strategy towards regulation of EDCs in water resources worldwide. The main recommendations include 1) opting for internationally validated cell reporter in vitro bioassays to reduce animal use & cost; 2) testing for cell viability (a critical parameter) when using in vitro bioassays; and 3) evaluating the recovery of the water sample preparation method selected. This review also highlights future research avenues for the EDC screening revolution (e.g., 3D tissue culture, transgenic animals, OMICs, and Adverse Outcome Pathways (AOPs)). ; This work was supported by the Fonds de recherche du Québec - Nature et technologies (FRQNT-290501) to JR, Natural Sciences and Engineering Research Council (NSERC) of Canada (NSERC-DG-2020-06475), and Canada Research Chairs to VSL (CRC-950-232235). LNM was supported by a H2020-Marie Skłodowska-Curie Action MSCA-IF-RI- 2017 awarded by the European Commission (ref. 797725-EpiSTOX). The authors are grateful to the Intersectorial Centre for Endocrine Disruptor Analysis (ICEDA)'s researcher network that facilitated this Special Issue. We thank Peta Neale that compiled references from the literature for EBT value that can be found in Table 3. ; Peer reviewed