HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Metabolic resistance of the tiger mosquito to pyrethroid insecticides in La Réunion Island likely results from local adaptation
No full textAbstract The resistance of mosquitoes to insecticides is a valuable model system for studying the genetic bases of xenobiotic adaptation in insects. The spread of the Asian tiger mosquito Aedes albopictus combined to the massive use of pyrethroid insecticides to limit arbovirus transmission resulted in the rise of resistance in various continents. Here, we investigated the genetic mechanisms underlying the recent adaptation of this mosquito to deltamethrin in La Réunion island. Bioassays confirmed the presence of resistance alleles in field populations. The resistance phenotype was further enhanced in the laboratory following a few generations of controlled selection. Combining whole genome Pool-seq and RNA-seq revealed no evidence of target-site resistance mutations but the over-expression and variant selection of detoxification enzymes associated with pyrethroid metabolism including cytochrome P450s, transferases and ABC-transporters. Among over-expressed detoxification genes, only one was linked to a gene duplication while polymorphism data suggest most of them being trans-regulated. Genome-wide selection signatures revealed a 9 Mb inverted superlocus responding to insecticide selection whose phenotypical importance remains uncertain. Altogether, this study indicates that the multigenic metabolic resistance phenotype observed in this insular territory mainly results from local adaptation. From an applied perspective, this study provides a set of markers to track pyrethroid resistance in the tiger mosquito in the South-West Indian Ocean. As this region is subjected to recurrent arbovirus outbreaks, the additive resistance phenotype that may arise from the introduction of Kdr mutations from other territories also calls for improving resistance surveillance at the regional scale. Author summary While novel vector control strategies are being developed, chemical insecticides remain widely used to control mosquitoes transmitting human diseases such as the Asian tiger mosquito. However, the recurrent use of insecticides resulted in the emergence of resistance which can ultimately affect vector control efficacy. Here, we investigate the genetic bases underlying the resistance of the Asian tiger mosquito to the pyrethroid insecticide deltamethrin in La Réunion island. By combining two complementary genomic approaches, we showed that resistance is mainly caused by an increased insecticide detoxification while classical ‘Knock down resistance’ mutations affecting the target of the insecticide were not detected. We also showed that resistance is underlain by multiple genetic changes spread across the genome, supporting the local selection of resistance rather than the introduction of resistance alleles. Furthermore, we identified a large inverted supergene responding to insecticide selection. This study provides valuable insights into the genetic bases of insecticide resistance, enabling the implementation of molecular makers to improve the tracking of insecticide resistance in this major mosquito vector across the Indian Ocean
Absence of phagolysosomal activation and high clearance efficiency define the low pulmonary toxicity of short asbestos fibers
No full textInternational audienceThe physicochemical properties of fibers critically determine asbestos pathogenicity, driving inflammation, fibrosis, and lung cancer. The prevailing paradigm in fiber toxicology posits that long and biopersistent fibers pose a greater health risk than short fibers. However, this assumption is debated due to limited studies specifically assessing the pathogenicity of short fibers. In this study, we compared the lung proinflammatory and profibrogenic effects of two amosite fiber types, long pristine amosite (pAmo, L > 5 µm) and short milled amosite (mAmo, L < 5 µm). In instilled C57BL/6 mice, long pAmo were significantly more inflammogenic and fibrogenic than short mAmo, which only induced limited acute pulmonary toxicity. Radical production under acidic phagolysosomal conditions occurred with long pAmo but not mAmo, explaining the pronounced pulmonary responses to pAmo. ICP-MS analysis revealed that long pAmo persisted in lung tissue, whereas short mAmo was completely cleared within four months. Nevertheless, a substantial fraction of short mAmo was biodistributed to extrapulmonary organs, including liver, spleen, and mediastinal lymph nodes in comparison to long pAmo. In conclusion, these findings establish fiber length as a critical determinant of asbestos-induced pulmonary pathogenicity and demonstrate that the limited pulmonary toxicity of short amosite fibers results from their low reactivity and rapid lung clearance. Moreover, the significant extrapulmonary translocation of short amosite observed in our study underscores the importance of considering the potential systemic effects of small fibers
Human and zebrafish mineralocorticoid receptors reporter cell assays to assess the activity of chemicals
No full textInternational audienceThe action of environmental chemicals (ECs) on the mineralocorticoid receptor (MR) has beensuggested to impair physiological processes regulated by this nuclear receptor. However, it remainsunderstudied both as target of ECs and with respect to potential species-specific differences. In thisregard, we have developed reporter cell lines to identify the response to different steroids, ECs andurban wastewater (WW) sample extracts of human MR (hMR) and zebrafish MR (zfMR). Most of thesteroids had a higher efficacy on zfMR than hMR while the ECs were antagonists to both hMR andzfMR, with a lower potency on the latter. Interestingly, WW sample extracts revealed the presence ofMR activity with a greater activity on zfMR compared to hMR, suggesting the presence of steroids inWW. These screening tools have proven to be powerful tools for characterizing the interaction ofchemicals with MRs and revealing their presence in environmental samples
Endocrine effects of Imazalil on aromatase expression, vitellogenesis and ovarian histology using cyp19a1a-eGFP-casper transgenic zebrafish
No full textInternational audienceConsidering the hazards and risks posed by endocrine disrupting chemicals (EDC) to organisms, there is a need to study their effects. To that end, transgenic fish are powerful models that can provide mechanistic information regarding the endocrine activity of test chemicals. In this study, we used a newly developed transgenic zebrafish line (cyp19a1a-eGFP-casper) in the OECD 21-day fish assay (OECD TG 230) to provide additional mechanistic insight on Imazalil (IMZ; 1.9; 9.9 and 140.7 μg/L). After 21 days of exposure to IMZ, the circulating concentrations of 17-β-estradiol (E2) and vitellogenin decreased in females, reflecting the aromatase activities inhibition. Exposure to 140.7 μg/L of IMZ for 21 days also resulted in a change in the proportion of the different oocyte stages in the ovaries, with an accumulation of large oocytes in exposed females. In addition to the classical endpoints, in vivo GFP fluorescence was quantified in the ovaries during the time course of the exposure to follow gonadal aromatase expression. After seven days of exposure, ovarian aromatase expression increased in females exposed to medium and high concentrations of IMZ, persisting over the 21-day of exposure in fish from the highest concentration group and reflecting a compensatory response to the aromatase enzymatic activities inhibition. Results from the present study provided valuable information on the mode of action and the effects of IMZ in zebrafish. Transgenic zebrafish exposure to IMZ caused a cascade of responses consistent with effects reported for wild-type fish exposed to azole fungicides, both qualitatively and quantitatively. The cyp19a1a-eGFP (-casper) transgenic zebrafish lines, allowed in vivo monitoring of gonadal aromatase expression in a time- and concentration-dependent manner thereby demonstrating their relevance to provide complementary mechanistic information on aromatase in regulatory assays such as OECD TG 230
Distribution spatiale et temporelle des éléments du groupe du platine dans les zones rurales de France métropolitaine à l'aide de mousses forestières
No full textInternational audienceAlthough emissions of platinum group elements (PGEs) have been increasing since the 1970s, their levels in rural areas are often considered negligible. We will demonstrate that there is long-distance contamination of forest ecosystems, and that palladium (Pd), platinum (Pt) and rhodium (Rh) levels are increasing over a 5-year period. PGEs levels were analyzed in mosses collected from 371 of the same forest sites in 2016 and 2021.Our results show that concentrations follow the order: Pd > Pt > Rh. Pd levels are all above the limits of quantification in 2016 and 2021, but they have increased over 5 years. Pt and Rh concentrations in mosses were respectively above the limit of quantification (LOQ) at 234 and 71 sites in 2016 and at 371 and 348 sites in 2021. We have shown that Pt is the element with the highest rate of increase, followed by Rh and Pd. This rate of change over 5 years correlates significantly with the initial concentration in 2016. A study of the Pt/Pd, Pt/Rh and Rh/Pd ratios shows a significant increase, confirming a greater increase in Pt and Rh than in Pd over the period.The study of spatial distribution tends to show that the sources of emissions of the elements are different. Nevertheless, it is necessary to work on the forms of PGEs emissions to gain a better understanding of their bioavailability and their impact on organisms, biodiversity and ecosystem functioning
Universal Electromagnetic Reference Skin Model for APD Evaluation at 6–100 GHz
No full textInternational audienceThe increasing use of the upper part of the microwave spectrum for wireless communications requires appropriate methods and instrumentation for user exposure assessment. In this context, the IEC TC106 is developing a new international standard for user exposure compliance testing of the next generation 5G/6G wireless devices operating above 6 GHz. As a part of this initiative, the development of a universal reference skin model (RSM) is fundamental for definition of reference data to be included in specifications for body phantom design. In this study, we systematically analyze the impact of the human body near-surface tissue structure on the electromagnetic field (EMF) reflection from the skin surface in the 6–100 GHz range. A conventional multi-layer model is used to calculate skin reflectance as a function of the tissue thickness for the range of thicknesses corresponding to that of typical human skin and near-surface body tissues at four body sites concerned by the 5G/6G wireless use-case scenarios, namely: head, torso, forearm, and palm. The dominant contribution from the epidermis/dermis (ED) layer to the skin reflectance is demonstrated for all body sites in the considered frequency range. A high variation in the reflectance of the palm skin at frequencies above 20 GHz is demonstrated and explained by the matching layer effect associated with a thick stratum corneum (SC). The dry skin model, represented by a semi-infinite homogeneous medium with complex permittivity equivalent to that of the ED tissue, is shown to be an appropriate RSM both for the experimental and numerical evaluation of the absorbed power density (APD) in the 6–100 GHz range. The reference data for the antenna loading and APD at the skin surface are provided for standard reference feeds at 10 GHz, 30 GHz, 60 GHz, and 90 GHz
PFAS exposure during pregnancy: Implications for placental health and functioning
No full textInternational audienceBackground: Animal studies have linked prenatal poly-and perfluoroalkyl substances (PFAS) exposures with impaired placental structure and function. In humans, only few studies have investigated such associations. Objective: We studied whether PFAS, individually and as a mixture, affected placental function. Methods: In 367 pregnant women, we quantified 13 PFAS in serum collected at 19.3 gestational weeks (median). Placental weight was recorded at delivery. Histological examination of placental tissues allowed estimation of vascular perfusion (percentage of villi with syncytial knots, capillary density, intervillous space) and placental aging (fibrin deposition, calcification). Associations between PFAS and each of these parameters were assessed using adjusted linear, logistic regressions and mixture modeling through cluster analysis and Bayesian kernel machine regression (BKMR). Results: PFHxPA quantification (yes versus no) was associated with an increase in the percentages of villi with syncytial knots (β = 6.0% [95% CI: 1.1; 11]) and reduced intervillous spaces (β = 4.7% [95% CI: 0.1; 9.3]). A similar pattern was observed with PFHpA. Isolated associations were observed between PFTrDA and percentages of villi with syncytial knots (β = 8.6% [95% CI: 2.2; 15]) and 6:2diPAP and capillary density (β = -17% [95% CI: -30; -4.6]). Cluster analysis suggested that women in the moderate-to-higher PFAS exposure group had on average lower placental weight (β= -30 g [95% CI: -56; -4.3]), compared to those in the lower exposure group. Conclusions: Pregnancy PFAS levels were associated with placental parameters of fetal-maternal exchange, highlighting their broad physiological impacts
Longitudinal associations between household use of "green" cleaning products and asthma symptoms
No full textInternational audienceBACKGROUND: The household use of irritant and sprayed cleaning products is an established asthma risk factor, which could motivate consumers to turn to "green" products. However, only two cross-sectional studies, with inconsistent results, evaluated the potential respiratory health impacts of "green" products. OBJECTIVE: We investigated 2-years effects on asthma of household use of "green" products and irritants/sprays, using longitudinal data from the French NutriNet-Santé cohort. METHODS: The asthma symptom score and household use of "green" products and irritants/sprays were evaluated using standardized questionnaires in 2018 and 2020. The evolution of weekly use (persistent, increased versus no weekly use) was studied in association with (i) the asthma symptom score in 2020; (ii) the incidence of asthma symptoms between 2018-2020 (incidence vs. asymptomatic); (iii) the evolution of asthma symptoms between 2018-2020 (improvement, deterioration vs. symptomatic stable) by logistic regressions. Models were adjusted for sex, age, smoking status, body mass index, educational level, and use of irritants/sprays (for "green" products). RESULTS: Our study was based on 30,012 adults (mean age: 49 years(sd:14), 74% women). For irritants/sprays, a persistent (40%) and an increased (26%) use was associated with asthma symptoms (Mean Score Ratio(MSR)=1.26[1.18-1.34] and MSR=1.14[1.06-1.22], respectively), incidence (OR=1.30[1.16-1.45] and OR=1.07[0.95-1.20]), and deterioration (OR=1.48[1.19-1.85] and OR=1.28[1.01-1.64]). For green products, a persistent (20%) and an increased (12%) use was associated with symptoms in 2020 (MSR=1.08[1.01-1.16] and MSR=1.07[0.99-1.16]), and associations were suggested with incidence (OR=1.09[0.97-1.22] and OR=1.11[0.97-1.27]). CONCLUSION: Persistent and increased use of irritants/sprays but also "green" products was associated with deleterious effects on asthma over time
Exposure Perception and Symptom Reporting in Idiopathic Environmental Intolerance Attributed to Electromagnetic Fields Using a Co‐Designed Provocation Test
No full textInternational audienceIdiopathic Environmental Intolerance Attributed to Electromagnetic Fields (IEI‐EMF) is a syndrome that defines people who report symptoms that they attribute to their exposure to EMF sources, without any identified underlying medical condition to explain these symptoms. To date, provocation protocols have failed to demonstrate a consistent relationship between EMF exposure and reported symptoms, raising questions among some researchers and individuals with IEI‐EMF about the relevance of these protocols for studying the syndrome. To address these criticisms, a provocation protocol was co‐designed in collaboration with individuals with IEI‐EMF. This study presents the results of the tests, with a focus on exposure perception and symptom reporting among IEI‐EMF volunteers. A total of 47 IEI‐EMF volunteers were enrolled and participated in an open‐field habituation session. Of these, 27 completed the first double‐blind controlled exposure session, while 26 and 16 volunteers, respectively, participated in three sessions for collective analyses and 12 sessions for individual‐level analyses. At the individual level, no consistent association was found between exposure perception certainty level and exposure status, except for one volunteer whose perception was mostly consistent with exposure status. Similarly, symptom reporting did not align with exposure status, except for the same volunteer, whose symptom reporting showed a borderline significant result with exposure status. However, for half of the volunteers, symptom reporting was significantly correlated with exposure perception certainty level, supporting a nocebo hypothesis. At the collective level, no consistency was observed between exposure perception certainty level, symptom reporting, and exposure status. This study discusses the conditions necessary for future provocation protocols to enhance their relevance, acceptability, and potential utility in a possible care‐oriented approach. It also considers criticisms of using exposure perception and symptom reporting as outcomes in provocation protocols, despite their central role in how individuals identify themselves as individuals with IEI‐EMF
Asymmetric flow field-flow fractionation coupled with inductively coupled plasma mass spectrometry for quality control of the grafting state of polystyrene on gold nanoparticles
No full textInternational audienceNanoplastics are omnipresent not only in the environment, but can also be transmitted to humans, mainly via the food chain and by contaminating respiratory air. These pollutants have the ability to cross biological barriers, carried into the bloodstream and reach different organs. In order to better understand the mechanisms of their uptake and transport into human cells and better assess their potential risks, the ability to localize and quantify nanoplastics in biological material is crucial. Electron microscopy (EM) represents a common method to study the uptake and intracellular fate of nanoparticles. However, polymeric materials are more difficult to visualize in cells due to the low contrast with cellular components. In this work, approximately 20 nm gold nanoparticles grafted onto polystyrene were synthesized as a model of metal-polymer hybrid nanoparticles in order to resolve the problem of low contrast and visualize nanoplastic-like particles in cells. A multi-technique approach has been developed to characterize those particles. Asymmetric flow field flow fractionation coupled with inductively coupled plasma mass spectrometry (AF4-ICP-MS) is presented as a control quality technique to characterize the grafting percentage of polystyrene onto gold nanoparticles as well as the grafting distribution and the concentration of the synthetized nanoparticles. Thus, grafting percentage of (57 ± 2)% and (100 ± 1)% were obtained for the two samples of Au@PS nanoparticles, respectively synthesized initially and after optimization of the synthesis process. Complementarily, Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) were used jointly with AF4-ICP-MS in order to determine the particles size and get complementary information about the grafting state. Thus, hydrodynamic diameters of (26 ± 1) nm and (35 ± 3) nm were found for the synthesized Au@PS nanoparticle samples