HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Ambient air pollution and childhood obesity from infancy to late childhood: An individual participant data meta-analysis of 10 European birth cohorts
No full textInternational audienceAmbient air pollution may contribute to childhood obesity through various mechanisms. However, few longitudinal studies examined the relationship between pre- and postnatal exposure to air pollution and obesity outcomes in childhood. We aimed to investigate the association between pre- and postnatal exposure to air pollution and body mass index (BMI) and the risk of overweight/obesity throughout childhood in European cohorts. This study included mother-child pairs from 10 European birth cohorts (n = 37111 (prenatal), 33860 (postnatal)). Exposure to nitrogen dioxide (NO2) and fine particulate matter with aerodynamic diameter < 2.5 µm (PM2.5) was estimated at the home addresses during pre- and postnatal periods (year prior outcome assessment). BMI z-scores (continuous) and overweight/obesity status (categorical: zBMI≥+2 (<5 years) or ≥+1 (≥5 years) standard deviations) were derived at 0-2, 2-5, 5-9, 9-12 years. Associations between air pollution exposure and zBMI were estimated separately for each pollutant and cohort using linear and logistic longitudinal mixed effects models, followed by a random-effects meta-analysis. The overweight/obesity prevalence ranged from 12.3-40.5 % between cohorts at 0-2 years, 16.7-35.3 % at 2-5 years, 12.5-40.7 % at 5-9 years, and 10.7-43.8 % at 9-12 years. Results showed no robust associations between NO2 exposure and zBMI or overweight/obesity risk. Exposure to PM2.5 during pregnancy was associated with 23 % (95%CI 1.05;1.37) higher overweight/obesity risk across childhood, and higher zBMI and overweight/obesity risk at 9-12 years. Heterogeneity between cohorts was considerable (I2:25-89 %), with some cohort-specific associations; e.g., pre- and postnatal exposure to PM2.5 was associated with lower zBMI across age periods in UK cohorts (ALSPAC and BiB), while postnatal exposure to PM2.5 and NO2 was associated with higher zBMI in one Dutch cohort (Generation R). Overall, this large-scale meta-analysis suggests that prenatal PM2.5 exposure may be associated with adverse childhood obesity outcomes, but provides no evidence to support an effect of postnatal air pollution exposure, although cohort-specific associations were observed
Associations between agricultural use of pyrethroid insecticides and asthma: AGRICAN cohort results
No full textInternational audienceRATIONALE: Following the withdrawal of organochlorines and organophosphates, pyrethroids have become the most used insecticides in both agricultural and domestic settings. OBJECTIVES: We analyzed data from the French AGRICAN agricultural cohort to assess associations of occupational pyrethroid exposures and allergic/non-allergic asthma. METHODS: At enrollment, asthma diagnosed by a doctor was reported by 11 815 participants (7028 classified as non-allergic and 4458 as allergic based on the presence of eczema and/or hay fever). Individual exposures to 17 pyrethroids were defined in 124 992 participants, based on a combination of the history of pesticide treatment of 11 crops (grassland, vineyard, wheat/barley, corn, field peas, potatoes, tobacco, beets, sunflower, rape, fruits) and a crop-exposure matrix. MEASUREMENTS AND MAIN RESULTS: In men, no association was observed for any of the pyrethroids regardless of asthma phenotype. In contrast, in ever-exposed women, asthma risk was increased with use of any pyrethroid, both for allergic (+80 %) and non-allergic asthma (+40 %). Highest increases were observed for allergic asthma with fenpropathrin (OR = 2.00; 95 %CI:1.38-2.90), tralomethrin (OR = 1.81; 95 %CI:1.28-2.56), fenvalerate (OR = 1.81; 95 %CI:1.38-2.38), permethrin (OR = 1.78; 95 %CI:1.26-2.50) and deltamethrin (OR = 1.76; 95 %CI:1.35-2.29). Stratified analyses on women who reported living on a farm in early life showed stronger associations for non-allergic asthma. For women who reported early life living on vineyards associations with pyrethroids were stronger for both allergic and non-allergic asthma. Associations for women who lived on cattle farms were reduced for some pyrethroids. CONCLUSION: Occupational pyrethroid exposure was positively associated with both allergic and non-allergic asthma in women but not in men
Energy metabolism rewiring following acute UVB irradiation is largely dependent on nuclear DNA damage
No full textInternational audienceSolar ultraviolet B (UVB) radiation-induced DNA damage is a well-known initiator of skin carcinomas. The UVB-induced DNA damage response (DDR) involves series of signaling cascades that are activated to maintain cell integrity. Among the different biological processes, little is known about the role of energy metabolism in the DDR.We sought to determine whether UVB-induced nuclear and/or mitochondrial cyclobutane pyrimidine dimers (CPDs) alter cellular energy metabolism. To gain insight into this question, we took advantage of keratinocytes expressing nuclear or mitochondrial CPD photolyase. Applying a quantitative proteomic approach and targeted metabolomics, we observed biphasic alterations in multiple metabolic pathways and in the abundance of various metabolites, largely influenced by the presence of genomic CPDs. The heightened oxygen consumption rate post-irradiation, along with mitochondrial structural rearrangements, was found to be dependent on both mitochondrial and nuclear CPDs.Understanding the influence of nuclear and mitochondrial DNA damage on keratinocyte responses to UVB irradiation deepens current knowledge regarding skin cancer prevention, initiation, and therapy
Profiles of the maternal occupational exposome during pregnancy and associations with intrauterine growth: analysis of the French Longitudinal Study of Children – ELFE study
No full textInternational audienceBackground: Numerous agents in the workplace are suspected of impairing fetal growth. To date, no epidemiological studies have specifically described the occupational exposome during pregnancy.Objective: The objectives were to determine maternal occupational exposome profiles and study their associations with intrauterine growth characteristics measured by small for gestational age (SGA), birthweight (BW), and head circumference (HC).Methods: We used data from the French national ELFE cohort. Occupational exposures to 47 agents (chemical, physical, biological, biomechanical, organizational and psychosocial), were identified using job exposure matrices. Mothers were classified as occupationally not exposed, uncertainly exposed, or exposed depending on their probability of exposure. Outcomes of interest were BW, SGA and HC. Maternal profiles of the occupational exposome were determined using hierarchical clustering of principal components. Associations between profiles and intrauterine growth outcomes were studied using linear or logistic regression models adjusted for potential confounders. Analyses were carried out depending on whether mothers stopped working during pregnancy.Results: The 12,851 included women were exposed to a median of 6 factors. Four occupational exposome profiles were identified, characterized by \"low exposure, stress at work\"; \"strenuous, high organization, low decision\"; \"postural constraints, psychosocial factors\", \"postural and strength constraints, chemical and biological factors\". In multivariate analyses, and among women who stopped working during the third trimester of pregnancy, analyses found associations between the profile \"postural constraints, psychosocial factor\" and SGA, and HC. None of the other exposure profiles were statistically significantly associated with foetal growth outcomes.Conclusion: The results show that the specific profile \"postural constraints, psychosocial factors\" may increase the risk of foetal growth retardation. Although these results need to be replicated, this study provides a first better understanding of the exposome of pregnant women at the workplace which may help to better adapt prevention strategies
Development of an LC-MS/MS method for the simultaneous quantification of 11 perfluoroalkyl compounds in mouse plasma for toxicokinetic applications
No full textInternational audienceFollowing regulatory pressure, the manufacture of long-chain per- and polyfluoroalkyl substances (PFAS) has been phased out, and alternatives such as short-chain homologs and ether-PFAS have replaced the bioaccumulative long-chain PFAS. However, data are lacking regarding the toxicokinetic (TK) properties of certain PFAS, particularly emergent substitutes for long-chain compounds. Additionally, the existing analytical methods used for TK studies measure a single compound or only a few simultaneously. For this reason, an LC-MS/MS method was developed for the simultaneous quantification in mouse plasma of 11 PFAS representative of some of the most important categories of these compounds, for application in TK studies. The method was successfully validated in the range of 0.5-1000 ng/mL, in accordance with the European Medicines Agency guidelines, and applied to a 24-h pilot TK study conducted in mice. All compounds were monitored over 24 hours in the pilot study. The present method is therefore suitable for the simultaneous quantification of PFAS in plasma samples and can be applied for future TK studies
Associations between individual and geospatial characteristics and power of 4G signals received by mobile phones
No full textInternational audienceBackground: The Received Signal Strength Indicator (RSSI) measures downlink signal intensity received by smartphones in 4th Generation LTE networks.Objective: This study evaluated how individual, technical, and spatial factors influenced LTE-RSSI during daily activities.Methods: Between November 2022 and October 2023, adults in France used the XMobiSensePlus Android smartphone application to record RSSI and GPS data. Distance to the operator's nearest antenna, obtained from Cartoradio, population and antenna density and urbanicity were analyzed using a geographic information system. Determinants of RSSI were assessed using an autoregressive mixed model incorporating restricted cubic splines for distance. Environmental exposures were estimated at 1800 MHz using conversion factors.Results: From 1,969,913 records of 187 participants, with measurements taken every 30 s over 7.9 days, the average LTE-RSSI was -79.3 dBm. The estimated electric field strength was 0.12 V/m, albeit with large uncertainty. The median distance to the nearest antenna was 536 m. Proximity to antennas increased RSSI. Antenna density positively influenced RSSI (overall β = +0.37 dBm per additional antenna per km2). Lower RSSI was observed in the evening and night, particularly in urban areas. Smartphone's technical parameters (Android version and System-on-a-Chip) influenced RSSI, operators did not. Proximity to antennas had greater impact in rural areas.Conclusion: Urbanicity, distance to the nearest 4G antenna, antenna density, time of day, and smartphone's technical parameters influenced RSSI levels in 4G networks in France, but not operator
Park7 (DJ-1), a Parkinson-associated glyoxalase/deglycase: characterization of enzymatic activity in biological samples using fluorescence-based liquid chromatography
No full textInternational audienceGlycation is an inevitable nonenzymatic covalent reaction between nucleophilic groups in proteins and nucleotides, and endogenous reducing sugars or dicarbonyls (e.g., methylglyoxal) leading to protein and/or nucleotide covalent modifications. This process initiates a series of dehydrations, oxidations and rearrangements that lead to a myriad of products called advanced glycation end products (AGEs). Previously, we showed that Park7 (or DJ-1) is a protein deglycase that repairs methylglyoxal-glycated biomolecules by acting on early glycation intermediates and releasing the repaired biomolecule and lactate. Moreover, the PARK7 gene is associated with recessive and sporadic forms of Parkinson's disease (PD). Thus, over the last few years, the function of Park7 has become an important research topic for understanding the etiology of PD. In this context, the development of sensitive enzymatic assays is crucial to quantify the activity of Park7 and develop specific modulators. Here, we describe a new method for measuring Park7 activity based on the separation and quantification of glycated and unglycated fluorescent nucleotides by Liquid Chromatography (LC). Kinetic and mechanistic analyses using human recombinant Park7 confirmed the reliability of this approach. In addition, this assay was further validated using cellular lysates. Our results indicate that this novel Park7 assay is simple, sensitive, and specific
In-flow single particle detection of sub-100 micron microplastics
No full textInternational audienceThe pervasive and growing contamination of ecosystems by microplastics (MPs) has emerged as a critical environmental and societal challenge. These synthetic polymer fragments, typically defined as plastic particles smaller than 5 mm, are now recognized not only for their persistence in natural environments but also for their potential to carry adsorbed pollutants and to be ingested by a wide range of organisms, including humans. Of particular concern are MPs in the sub-100 μm range, which are more difficult to isolate and analyze but may exhibit enhanced mobility, reactivity, and bioavailability. The accurate detection, quantification, and chemical characterization of such small MPs are therefore essential for advancing our understanding of their sources, fate, and impacts. However, current analytical approaches—primarily based on filtration, staining, and spectroscopic methods—remain time-consuming and often lack the sensitivity or selectivity required for sub-100 μm particles in complex aqueous matrices. In this study, we present a novel microfluidic strategy for the rapid, in-flow detection and molecular identification of individual MPs in suspension. The method integrates dielectrophoresis (DEP) for the label-free spatial manipulation of particles and Raman microspectroscopy (RM) for their chemical fingerprinting. A custom-fabricated glass microfluidic chip was developed, incorporating electrodes on both the top and bottom surfaces of the main channel to achieve three-dimensional DEP focusing. MPs ranging from 25 to 50 μm in diameter were successfully aligned along the channel's central axis and interrogated in real time using RM. This approach enabled unambiguous, particle-by-particle identification of five widely encountered polymer types: polystyrene (PS), polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), and polyethylene terephthalate (PET), both in monodisperse and polydisperse mixtures. Our results demonstrate that DEP/RM coupling offers a powerful and scalable platform for in-flow MPs analysis, combining high spatial resolution and chemical specificity. This proof of concept opens new possibilities for high-throughput and automated detection of MPs in environmental monitoring and water analysis
Quantitative HPLC-mass spectrometry analysis shows the drastic impact of the composition of aqueous and biochemical media on the release of soluble hydrolysis products from submicron polycaprolactone
No full textInternational audienceAccumulation of micro- and nanoplastics in the environment is a major concern, and biodegradable polymers are receiving growing interest as an alternative to more stable material. It remains yet to identify the degradation products of biodegradable plastics. In the present work, we studied polycaprolactone (PCL), a polymer used in a growing number of packaging and medical applications. We gathered quantitative data on the release of soluble oligomers from submicrometric PCL particles (100 to 1000 µm in diameter) throughout their degradation. This was made possible by the synthesis of well-characterized PCL oligomers, which were then used for the development of HPLC-mass spectrometry methods. The assay was first applied to degradation studies performed in aqueous media, in relationship to environmental degradation. We observed an influence of temperature and salinity, and obtained specific information on the mechanism of release of PCL hydrolysis products at the sub micrometric scale. The same approach was then applied to study PCL degradation in cell culture media used in toxicity studies, Oligomers arising from the hydrolysis of PCL particles were released in both the presence and the absence of cells. The size distribution under these conditions was shifted to shorter oligomers than in water. This observation, supported by experiments on synthetic PCL oligomers, pointed to a significant contribution of fetal calf serum used as an additive in cell culture medium. The bulk of these results show that hydrolysis of submicrometric PCL particles and the subsequent production of oligomers is an efficient process that is strongly modulated by the degradation medium
Rôle des interactions entre diatomées et hyphomycètes dans la décomposition de la matière organique en conditions stressantes (carence nutritive, fongicide)
No full textInternational audienceLes microorganismes des cours d'eau, notamment les diatomées, les hyphomycètes aquatiques et les bactéries, jouent un rôle central dans la décomposition de la litière végétale. Pourtant, l’impact des stresseurs environnementaux sur la colonisation microbienne et les processus de décomposition reste encore mal connu. Cette étude vise à évaluer dans quelle mesure une exposition préalable des communautés de microorganismes à des stresseurs affecte leur capacité de colonisation de la litière et in fine la dynamique de décomposition de celle-ci. Pour ce faire, différentes souches d’hyphomycètes et de diatomées ont été acclimatées en conditions stressantes (carences en azote et en phosphore ou exposition à 10 µg/L de tébuconazole, un fongicide). Ces différentes souches ont ensuite été utilisées pour constituer quatre assemblages microbiens : (i) bactéries seules (filtrats de cultures), (ii) bactéries-diatomées, (iii) bactéries-hyphomycètes, et (iv) un assemblage complet (bactéries, diatomées, hyphomycètes). Par la suite, chaque assemblage a été mis en contact, en conditions non stressantes, avec des disques de feuilles d’érable stériles pendant 1,5 j. Enfin, les disques ont été récupérés et incubés pendant 30 j, toujours en conditions non stressantes. Des échantillonnages ont été réalisés à 1,5, 10 et 30 j pour caractériser l’évolution temporelle des disques de feuilles (taux de décomposition, ratios élémentaires C:N:P) et la composition des communautés microbienne ayant colonisé les feuilles (imagerie, qPCR).Les premiers résultats indiquent un effet significatif de la composition initiale des assemblages microbiens sur la décomposition, avec une efficacité accrue lorsque diatomées et hyphomycètes sont combinés, suggérant une complémentarité fonctionnelle entre ces groupes. L’analyse stœchiométrique montre également des effets différenciés des assemblages sur la dynamique de fixation de l’azote et du phosphore dans les feuilles. En revanche, les conditions stressantes appliquées en phase de culture ne semblent pas altérer significativement les capacités de décomposition, suggérant une résilience des communautés microbiennes ou des mécanismes de récupération. Les analyses d’imagerie (profilométrie) et qPCR sont en cours pour caractériser la succession microbienne et identifier les mécanismes de colonisation différenciée. Ces résultats contribueront à améliorer la compréhension des liens entre structure des communautés microbiennes et processus de décomposition dans un contexte de stress environnemental