HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Pre- and early post-natal exposure to phthalates and DINCH in a new type of mother-child cohort relying on within-subject pools of repeated urine samples
No full textInternational audienceFor non-persistent chemicals such as phthalates, a single spot urine sample only reflects exposure in the past few hours. Collecting repeated urine samples for each participant over windows of sensitivity is expected to improve exposure characterization but has rarely been done. We aimed to rely on within-subject pools of repeated urine samples to assess phthalate exposure during pregnancy and infancy. Women of the French SEPAGES mother-child cohort were asked to collect three urine samples per day over seven consecutive days, twice during their pregnancy (approximatively second (T2) and third (T3) trimesters). For their infants they also collected one sample per day during a week at two (M2) and twelve months (M12). Samples were pooled (within-subject, within-period) prior to phthalate and DINCH metabolite concentrations assessment. Number of pooled samples assayed was 477, 456, 152 and 100 for T2, T3, M2 and M12, respectively. All metabolites were detected in more than 95% of the pooled samples except for the two DINCH metabolites (oh- and oxo-MINCH), MMCHP and oh-MPHP at M2 for which detection frequencies ranged between 64% and 88%. Maternal concentrations of MiBP, MBzP, DEHP metabolites and oxo-MiNP decreased between 2014 and 2017, whereas concentrations of oh-MiNP and the two DINCH metabolites increased (Mann-Kendall p-values < 0.05). While improved compared to studies that relied on spot samples, Intraclass Correlation Coefficients for the pregnancy were below 0.40 for most metabolites. Spearman correlation coefficients between pooled samples collected in infancy were lower than those observed during pregnancy, and were all below 0.30. Exposure to emerging phthalate substitutes such as DINCH and DPHP seems widespread among pregnant women and infants. Collecting repeated urine samples in pregnant women and infants is feasible. The relatively low correlation across trimesters and between maternal and infant samples highlights the need to collect biospecimens in the assumed sensitive time window
Exposure to radiofrequency electromagnetic fields: Comparison of exposimeters with a novel body-worn distributed meter
No full textInternational audienceBackground: Exposure to radiofrequency electromagnetic fields (RF-EMF) is often measured with personal exposimeters, but the accuracy of measurements can be hampered as carrying the devices on-body may result in body shielding. Further, the compact design may compromise the frequency selectivity of the sensor. The aim of this study was to compare measurements obtained using a multi-band body-worn distributed-exposimeter (BWDM) with two commercially available personal exposimeters (ExpoM-RF and EmeSpy 200) under real-life conditions.Methods: The BWDM measured power density in 10 frequency bands (800, 900, 1800, 2100, 2600 MHz, DECT 1900 MHz, WiFi 2.4 GHz; with separate uplink/downlink bands for 900, 1800 and 2100 MHz); using 20 separate antennas integrated in a vest and placed on diametrically opposite locations on the body, to minimize bodyshielding. RF-EMF exposure data were collected from several microenvironments (e.g. shopping areas, train stations, outdoor rural/ urban residential environments, etc.) by walking around pre-defined areas/routes in Belgium, Spain, France, the Netherlands and Switzerland. Measurements were taken every 1-4 s with the BWDM in parallel with an ExpoM-RF and an EmeSpy 200 exposimeter. We calculated medians and interquartile ranges (IQRs) and compared difference, ratios and correlations of geometric mean RF-EMF exposure levels per microenvironment as measured with the exposimeters and the BWDM.Results: Across 267 microenvimnments, medians and IQR of total BWDM measured RF-EMF exposure was 0.13 (0.05-0.33) mW/m(2). Difference: IQR of exposimeters minus BWDM exposure levels was -0.011 (-0.049 to 0.0095) mW/m(2) for the ExpoM-RF and -0.056 (-0.14 to -0.017) for the EmeSpy 200; ratios (exposimeter/BWDM) of total exposure had an IQR of 0.79 (0.55-1.1) for the ExpoM-RF and 0.29 (0.22-0.38) for the EmeSpy 200. Spearman correlations were 0.93 for the ExpoM-RF vs the BWDM and 0.96 for the EmeSpy 200 vs the BWDM.Discussion and conclusions: Results indicate that exposimeters worn on-body provide somewhat lower total RF-EMF exposure as compared to measurements conducted with the BWDM, in line with effects from body shielding. Ranking of exposure levels of microenvironments showed high correspondence between the different device types. Our results are informative for the interpretation of existing epidemiological research results
Differential impact of dose-range glyphosate on locomotor behavior, neuronal activity, glio-cerebrovascular structures, and transcript regulations in zebrafish larvae
No full textInternational audienceThe presence of glyphosate represents a debated ecotoxicological and health risk factor. Here, zebrafish larvae were exposed, from 1.5 to 120 h post-fertilization, to a broad concentration range (0.05-10.000 μg/L) of glyphosate to explore its impact on the brain. We evaluated morphology, tracked locomotor behavior and neurophysiological parameters, examined neuro-glio-vascular cell structures, and outlined transcriptomic outcomes by RNA sequencing. At the concentration range tested, glyphosate did not elicit gross morphological changes. Behavioral analysis revealed a significant decrease in locomotor activity following the exposure to 1000 μg/L glyphosate or higher. In parallel, midbrain electrophysiological recordings indicated abnormal, and variable, spike activity in zebrafish larvae exposed to 1000 μg/L glyphosate. Next, we asked whether the observed neurophysiological outcome could be secondary to brain structural modifications. We used transgenic zebrafish and in vivo 2-photon microscopy to examine, at the cellular level, the effects of the behavior-modifying concentration of 1000 μg/L, comparing to low 0.1 μg/L, and control. We ruled out the presence of cerebrovascular and neuronal malformations. However, microglia morphological modifications were visible at the two glyphosate concentrations, specifically the presence of amoeboid cells suggestive of activation. Lastly, RNAseq analysis showed the deregulation of transcript families implicated in neuronal physiology, synaptic transmission, and inflammation, as evaluated at the two selected glyphosate concentrations. In zebrafish larvae, behavioral and neurophysiological defects occur after the exposure to high glyphosate concentrations while cellular and transcript signatures can be detected in response to low dose. The prospective applicability to ecotoxicology and the possible extension to brain-health vulnerability are critically discussed
Investigation of steatosis profiles induced by pesticides using liver organ-on-chip model and omics analysis
No full textInternational audienceSeveral studies have reported a correlation between pesticides exposure and metabolic disorders. Dichlorodiphenyltrichloroethane (DDT) and permethrin (PMT), two pesticides highly prevalent in the environment, have been associated to dysregulation of liver lipids and glucose metabolisms and non-alcoholic fatty liver disease (NAFLD). However, the effects of DDT/PMT mixtures and mechanisms mediating their action remain unclear. Here, we used multi-omic to investigate the liver damage induced by DDT, PMT and their mixture in rat liver organ-on-chip. Organ-on-chip allow the reproduction of in vivo-like micro-environment. Two concentrations, 15 and 150 μM, were used to expose the hepatocytes for 24 h under perfusion. The transcriptome and metabolome analysis suggested a dose-dependent effect for all conditions, with a profile close to control for pesticides low-doses. The comparison between control and high-doses detected 266/24, 256/24 and 1349/30 genes/metabolites differentially expressed for DDT150, PMT150 and Mix150 (DDT150/PMT150). Transcriptome modulation reflected liver inflammation, steatosis, necrosis, PPAR signaling and fatty acid metabolism. The metabolome analysis highlighted common signature of three treatments including lipid and carbohydrates production, and a decrease in amino acids and krebs cycle intermediates. Our study illustrates the potential of organ-on-chip coupled to multi-omics for toxicological studies and provides new tools for chemical risk assessment
Individual Exposure to Environmental Radiofrequency Electromagnetic Fields in Hospitalized Preterm Neonates
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Long-term exposure to ambient air pollution and risk of dementia: Results of the prospective Three-City Study
No full textInternational audienceBACKGROUND: Emerging epidemiological evidence suggests a relationship between exposure to air pollution and dementia. However, most of the existing studies relied on health administrative databases for the diagnosis of dementia. In a large French population-based cohort (the 3C Study), we assessed the effects of particulate matter ≤2.5 µm (PM2.5), nitrogen dioxide (NO(2)) and black carbon (BC) on the risk of dementia diagnosed with reliable tools.METHODS: Participants aged ≥65 years were recruited between 1999 and 2001 and followed for 12 years. At baseline and every 2 years, dementia was suspected on the basis of the neuropsychological and neurological examination and confirmed by an independent committee of clinicians. Exposure to NO(2), BC and PM2.5 at the participants’ residential address was estimated using land use regression models. For each pollutant and year of follow-up, the 10-year moving average of past exposure was estimated. Multilevel spatial random-effects Cox proportional hazards models were used in which exposure was included as a time-varying variable. Analyses were adjusted for individual (age, sex, education, APOE4 genotype, health behaviours) and contextual (neighbourhood deprivation index) confounders.RESULTS: At baseline, the median age of the 7066 participants was 73.4 years, and 62% were women. The median follow-up duration was 10.0 years during which 791 participants developed dementia (n = 541 Alzheimer’s disease (AD) and n = 155 vascular/mixed dementia (VaD)). The 10-year moving average of PM2.5 concentrations ranged from 14.6 to 31.3 µg/m(3). PM2.5 concentration was positively associated with dementia risk: HR = 1.20, 95% CI (1.08-1.32) for all-cause dementia, 1.20 (1.09-1.32) for AD, and 1.33 (1.05-1.68) for VaD per 5 µg/m(3) PM2.5 increase. No association was detected between NO(2) or BC exposure and dementia risk.CONCLUSION: In this large cohort of older adults, long-term PM2.5 exposure was associated with increased dementia incidence. Reducing PM2.5 emissions might lessen the burden of dementia in aging populations
Pregnancy exposure to synthetic phenols and placental DNA methylation -An epigenome-wide association study in male infants from the EDEN cohort ☆
No full textInternational audienceIn utero exposure to environmental chemicals, such as synthetic phenols, may alter DNA methylation in different tissues, including placenta - a critical organ for fetal development. We studied associations between prenatal urinary biomarker concentrations of synthetic phenols and placental DNA methylation. Our study involved 202 mother-son pairs from the French EDEN cohort. Nine phenols were measured in spot urine samples collected between 22 and 29 gestational weeks. We performed DNA methylation analysis of the fetal side of placental tissues using the IlluminaHM450 BeadChips. We evaluated methylation changes of individual CpGs in an adjusted epigenome-wide association study (EWAS) and identified differentially methylated regions (DMRs). We performed mediation analysis to test whether placental tissue heterogeneity mediated the association between urinary phenol concentrations and DNA methylation. We identified 46 significant DMRs (>= 5 CpGs) associated with triclosan (37 DMRs), 2,4-dichlorophenol (3), benzophenone-3 (3), methyl- (2) and propylparaben (1). All but 2 DMRs were positively associated with phenol concentrations. Out of the 46 identified DMRs, 7 (6 for triclosan) encompassed imprinted genes (APC, FOXG1, GNAS, GNASAS, MIR886, PEG10, SGCE), which represented a significant enrichment. Other identified DMRs encompassed genes encoding proteins responsible for cell signaling, transmembrane transport, cell adhesion, inflammatory, apoptotic and immunological response, genes encoding transcription factors, histones, tumor suppressors, genes involved in tumorigenesis and several cancer risk biomarkers. Mediation analysis suggested that placental cell heterogeneity may partly explain these associations. This is the first study describing the genome-wide modifications of placental DNA methylation associated with pregnancy exposure to synthetic phenols or their precursors. Our results suggest that cell heterogeneity might mediate the effects of triclosan exposure on placental DNA methylation. Additionally, the enrichment of imprinted genes within the DMRs suggests mechanisms by which certain exposures, mainly to triclosan, could affect fetal development
Getting ready for a long bath: skin permeability decreases prior to aquatic breeding in male toads
No full textInternational audienceFish-farming can lead to eutrophication of freshwater environments through the increase in organic matter resulting from food supplementation and fish wastes. Eutrophication can induce an excessive development of plants and algae on various substrates, including living organisms (algal epibiosis). Although algal epibiosis has been shown to reduce mobility by increasing drag in marine species, its consequences on host species in freshwater ecosystems remain poorly known. In this study, we investigated the individual (age and sex) and environmental (extensive versus intensive fish-farming) determinants of epizoic algae presence and abundance on European pond turtles (Emys orbicularis). We also explored the potential consequences of algal epibiosis on fitness-related traits of E. orbicularis. Based on a large sample size (1112 turtles from 23 ponds), we found that the abundance of algae growing on turtles increased during spring and summer. However, such increase was different across ages and sex; presumably reflecting the influence of thermoregulation (required to increase metabolic rates to sustain growth and reproduction) and thus, periodical drying of the shell, in reducing algal cover. We also found that intensive fish-farming increased algal epibiosis, especially when fish-farming involved food supplementation. Finally, we found that adult female body condition and reproduction of turtles were negatively linked to algal cover, thereby suggesting a potential negative impact of algal fouling on some fitness-related traits of adult female turtles. Future studies should usefully assess the demographic consequences of algal epibiosis induced by fish farming in this long-lived vertebrate
A comparison of behavioral and reproductive parameters between wild-type, transgenic and mutant zebrafish: Could they all be considered the same “zebrafish” for reglementary assays on endocrine disruption?
No full textInternational audienceTransgenic zebrafish models are efficiently used to study the effects of endocrine disrupting chemicals (EDC);thereby informing on their mechanisms of action. However, given the reported differences between zebrafishstrains at the genetical, physiological and behavioral levels; care should be taken before using these transgenicmodels for EDC testing. In the present study, we undertook a set of experiments in different transgenic and/ormutant zebrafish strains of interest for EDC testing: casper, cyp19a1a-eGFP, cyp19a1a-eGFP-casper, cyp11c1-eGFP,cyp11c1-eGFP-casper. Some behavioral traits, and some biochemical and reproductive physiological endpointscommonly used in EDC testing were assessed and compared to those obtained in WT AB zebrafish to ensure thattransgene insertion and/or mutations do not negatively modify basal reproductive physiology or behavior of thefish.Behavioral traits considered as anxiety and sociality have been monitored. Sociality was evaluated bymonitoring the time spent near congeners in a shuttle box while anxiety was evaluated using the Novel tankdiving test. No critical difference was observed between strains for either sociality or anxiety level. Concerningreproduction, no significant difference in the number of eggs laid per female, in the viability of eggs or in thefemale circulating VTG concentrations was noted between the 5 transgenic/mutants and the WT AB zebrafishstudied.In summary, the transgene insertion and the mutations had no influence on the endpoints measured in basalconditions. These results were a prerequisite to the use of these transgenic/mutant models for EDC testing. Nextstep will be to determine the sensitivity of these biological models to chemical exposure to accurately validatetheir use in existing fish assays for EDC testing
