International audience | Aflatoxin B1 (AFB1) is the most potent natural carcinogen among mycotoxins. Versicolorin A (VerA) is a precursor of AFB1 biosynthesis and is structurally related to the latter. Although VerA has already been identified as a genotoxin, data on the toxicity of VerA are still scarce, especially at low concentrations. The SOS/umu and miniaturised version of the Ames test in Salmonella Typhimurium strains used in the present study shows that VerA induces point mutations. This effect, like AFB1, depends primarily on metabolic activation of VerA. VerA also induced chromosomal damage in metabolically competent intestinal cells (IPEC-1) detected by the micronucleus assay. Furthermore, results from the standard and enzyme-modified comet assay confirmed the VerA-mediated DNA damage, and we observed that DNA repair pathways were activated upon exposure to VerA, as indicated by the phosphorylation and/or relocation of relevant DNA-repair biomarkers (γH2AX and 53BP1/FANCD2, respectively). In conclusion, VerA induces DNA damage without affecting cell viability at concentrations as low as 0.03 μM, highlighting the danger associated with VerA exposure and calling for more research on the carcinogenicity of this emerging food contaminant.

International audience | Trichothecenes (TCT) are very common mycotoxins. While the effects of DON, the most prevalent TCT, have been extensively studied, less is known about the effect of other trichothecenes. DON has ribotoxic, pro-inflammatory, and cytotoxic potential and induces multiple toxic effects in humans and animals. Although DON is not genotoxic by itself, it has recently been shown that this toxin exacerbates the genotoxicity induced by model or bacterial genotoxins. Here, we show that five TCT, namely T-2 toxin (T-2), diacetoxyscirpenol (DAS), nivalenol (NIV), fusarenon-X (FX), and the newly discovered NX toxin, also exacerbate the DNA damage inflicted by various genotoxins. The exacerbation was dose dependent and observed with phleomycin, a model genotoxin, captan, a pesticide with genotoxic potential, and colibactin, a bacterial genotoxin produced by the intestinal microbiota. For this newly described effect, the trichothecenes ranked in the following order: T-2>DAS > FX > NIV ≥ DON ≥ NX. The genotoxic exacerbating effect of TCT correlated with their ribotoxic potential, as measured by the inhibition of protein synthesis. In conclusion, our data demonstrate that TCT, which are not genotoxic by themselves, exacerbate DNA damage induced by various genotoxins. Therefore, foodborne TCT could enhance the carcinogenic potential of genotoxins present in the diet or produced by intestinal bacteria.

International audience | Food additives are one major hallmark of ultra-processed food in the Western-diet, a food habit often associated with metabolic disorders. Among these additives, the whitener and opacifying agent titanium dioxide (TiO2) raises public health issues due to the ability of TiO2 nanoparticles (NPs) to cross biological barriers and accumulate in different systemic organs like spleen, liver and pancreas. However before their systemic passage, the biocidal properties of TiO2 NPs may alter the composition and activity of the gut microbiota, which play a crucial role for the development and maintenance of immune functions. Once absorbed, TiO2 NPs may further interact with immune intestinal cells involved in gut microbiota regulation. Since obesity-related metabolic diseases such as diabetes are associated with alterations in the microbiota-immune system axis, this raises questions about the possible involvement of long-term exposure to food-grade TiO2 in the development or worsening of these diseases. The current purpose is to review the dysregulations along the gut microbiota-immune system axis after oral TiO2 exposure compared to those reported in obese or diabetic patients, and to highlight potential mechanisms by which foodborne TiO2 NPs may increase the susceptibility to develop obesity-related metabolic disorders.

International audience | Pollinators have to cope with a wide range of stressful, not necessarily lethal factors limiting their performance and the ecological services they provide. Among these stressors are pesticides, chemicals that are originally designed to target crop-harming organisms but that also disrupt various functions in pollinators, including flight, communication, orientation and memory. Although all these functions are crucial for reproductive individuals when searching for mates or nesting places, it remains poorly understood how pesticides affect reproduction in pollinators. In this study, we investigated how a widely used fungicide, boscalid, affects reproduction in honey bees (Apis mellifera), an eusocial insect in which a single individual, the queen, fulfills the reproductive functions of the whole colony. Boscalid is a succinate dehydrogenase inhibitor (SDHI) fungicide mainly used on rapeseed flowers to target mitochondrial respiration in fungi but it is also suspected to disrupt foraging-linked functions in bees. We found that immature queen exposure to sublethal, field relevant doses of boscalid disrupted reproduction, as indicated by a dramatic increase in queen mortality during and shortly after the nuptial flights period and a decreased number of spermatozoa stored in the spermatheca of surviving queens. However, we did not observe a decreased paternity frequency in exposed queens that successfully established a colony. Queen exposure to boscalid had detrimental consequences on the colonies they later established regarding brood production, Varroa destructor infection and pollen storage but not nectar storage and population size. These perturbations at the colony-level correspond to nutritional stress conditions, and may have resulted from queen reduced energy provisioning to the eggs. Accordingly, we found that exposed queens had decreased gene expression levels of vitellogenin, a protein involved in egg-yolk formation. Overall, our results indicate that boscalid decreases honey bee queen reproductive quality, thus supporting the need to include reproduction in the traits measured during pesticide risk assessment procedures.

International audience | Polycyclic aromatic hydrocarbons (PAHs) have been shown to influence endogenous hormones levels in animal models, but little is known about the effects of their mixtures. For hormone measurements, hair analysis is a promising approach to provide information on long-term status of hormones. Herein we used hair analysis to assess the combined effects of 13 PAHs on steroid and thyroid hormones levels in a rat model. The PAH mixture was administered orally three times per week to female rats at doses of 0, 10, 20, 40, 80, 200, 400 and 800 μg/kg of body weight for each compound over a 90-day exposure period. Fourteen out of 36 analyzed hormones were detected in rat hair, including pregnenolone (P5), 17α-hydroxyprogesterone (17-OHP4), corticosterone (CORT), dehydroepiandrosterone (DHEA), androstenedione (AD), 3,3'-diiodo-L-thyronine (T2), 3,3',5-triiodo-L-thyronine (T3), and 3,5,3',5'-triiodo-L-thyronine (T4). The PAH mixture significantly elevated P5 and DHEA levels at the doses of 200 and 400 μg/kg but reduced T2 and T3 levels at the highest dose as compared to the control. While P5, DHEA, 17-OHP4 and AD concentrations exhibited inverted U-shaped dose responses, T2, T3 and T4 concentrations exhibited inverse linear dose responses, which are further confirmed by their relationships with hair hydroxylated PAHs (OH-PAHs) concentrations. Likewise, there were significant nonmonotonic relationships of hormone molar ratios (e.g., AD/17-OHP4 and DHEA/CORT ratios) with exposure intensity and OH-PAHs. Overall, our results demonstrate the capability of PAH mixtures to interfere with steroid and thyroid hormones in female rats.

International audience | Diffuse pollution of the environment by pesticides has become a major soil threat to non-target organisms, such as earthworms for which declines have been reported. However some endogeic species are still abundant and persist in intensively cultivated fields, suggesting they become tolerant to long-term anthropogenic pressure. We thus considered the working hypothesis that populations of Aporrectodea caliginosa earthworms from conventionally managed fields developed a tolerance to pesticides compared with those from organically managed fields. To investigate this hypothesis, we studied earthworm populations of the same genetic lineage from soils that were either lowly or highly contaminated by pesticides to detect any constitutive expression of differentially expressed molecular pathways between these populations. Earthworm populations were then experimentally exposed to a fungicide-epoxiconazole-in the laboratory to identify different molecular responses when newly exposed to a pesticide. State-of-the-art omics technology (RNA sequencing) and bioinformatics were used to characterize molecular mechanisms of tolerance in a non-targeted way. Additional physiological traits (respirometry, growth, bioaccumulation) were monitored to assess tolerance at higher levels of biological organization. In the present study, we generated the de novo assembly transcriptome of A. caliginosa consisting of 64,556 contigs with N50 = 2862 pb. In total, 43,569 Gene Ontology terms were identified for 21,593 annotated sequences under the three main ontologies (biological processes, cellular components and molecular functions). Overall, we revealed that two same lineage populations of A. caliginosa earthworms, inhabiting similar pedo-climatic environment, have distinct gene expression pathways after they long-lived in differently managed agricultural soils with a contrasted pesticide exposure history for more than 22 years. The main difference was observed regarding metabolism, with upregulated pathways linked to proteolytic activities and the mitochondrial respiratory chain in the highly exposed population. This study improves our understanding of the long-term impact of chronic exposure of soil engineers to pesticide residues.

International audience | Glass manufacturing operations lead to an increasing number of abandoned slag heaps contaminated with metallic trace elements (MTE). However, the relative influence of edaphic factors on the biodiversity of glasswork wastelands is still poorly understood although closely related to sustainable land management practices. Therefore, the objectives of this research were to provide new insights into glasswork wastelands through the investigation of (i) Orthoptera, diurnal Lepidoptera, plant communities, and (ii) abiotic parameters in the topsoils. To that end, biodiversity indices were computed from ecological inventories performed on the herbaceous layer. In addition, soil samples were taken from the topsoil layer (0-10 cm) to assess agronomic properties, actually (CEC-exchangeable) and potentially bioavailable MTE fractions (DTPA-extractable) and pseudo-total MTE contents. On the one hand, the studied site was able to support a substantially higher than excepted biodiversity with orthopteran assemblages similar to grasslands and a diurnal Lepidoptera diversity comparable to urban parks. We also noted a positive influence of plant richness on the diurnal Lepidoptera community structure. On the other hand, topsoil analysis revealed a severe Pb contamination (1800-3100 mg kg − 1) and a high potentially bioavailable Pb fraction (800-1300 mg kg − 1). However, CEC-exchangeable MTE concentrations were all below the analytical quantification limits. Moreover, the site was characterized by a medium soil fertility. From these results, Pb contamination does not appear to be a primary limiting factor for the establishment of these communities. We assume that glasswork wasteland ecosytems are more affected by soil fertility or land management practices. To conclude, these sites are able to provide biodiversity ecosystem services, acting as wildlife sanctuaries for Orthoptera and diurnal Lepidoptera, and strategic metals by phytoextraction in a circular economy model. Thus, wasteland management practices should consider the local-scale drivers of biodiversity in order to reach at least the zero net loss of biodiversity. ☆ This paper has been recommended for acceptance by Amit Bhatnagar.