Sex-dependent impact of perinatal 5G electromagnetic field exposure in the adolescent rat behavior

International audienceThe fifth generation (5G) network is currently being worldwide spread out, raising questions about the potential impact of this new technology, particularly on immature organisms. The current study aimed to investigate the effects of daily 5G electromagnetic field (EMF) perinatal exposure on the neurodevelopment of rats. The exposure level was set to the limit of whole-body public exposure defined by the International Commission on Non-Ionizing Radiation Protection. The mother rat specific absorption rate (SAR) was 0.07 W/kg for 22 h/day at 3500 MHz continuous wave from gestational day (GD) 8 to post-natal day (PND) 21. Clinical observations were performed on weight, length, sex ratio, number of pups per litter, and number of stillborn in sham and EMF-exposed groups (n = 7). The age of pinna ear detachment, incisor eruption, and eye opening were recorded. Behavior was assessed on righting, gripping, and negative geotaxis reflexes at PND 3 or 7 and on stereotyped and horizontal movements in the open field at PND 43. Our results indicated that both male and female pups showed delayed incisor eruption in the EMF-exposed group compared to the sham group (+ 1 day). Regarding activity in the open field, adolescent females showed less stereotyped movements (- 70%), while adolescent males showed more stereotyped movements (+ 50%) compared to the sham-exposed adolescent rats. Thus, the present study suggested that perinatal exposure to 5G at SAR level below reglementary threshold led to perturbations in the descendants seen in juveniles and adolescents

Etude des effets d’une exposition de type 5G sur le sommeil, la thermorégulation et les fonctions cardiovasculaire et thyroïdienne: EXSOCAR

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Dose- and Time-Dependent Effects of Radiofrequency Electromagnetic Field on Adipose Tissue: Implications of Thermoregulation and Mitochondrial Signaling

International audienceRecent studies have shed light on the effects of low-intensity radiofrequency (RF) fields on thermoregulation and adipose tissue metabolism. The present study aims to further explore these effects by analyzing the expression of thermoregulatory genes and investigating the involvement of mitochondria in adipose tissue metabolism. Male mice (n = 36 C57BL/6J) were assigned to either exposed or control groups. The exposed groups were subjected to RF fields at 900 MHz, with specific absorption rates (SAR) of 0.1 W/kg or 0.4 W/kg, either for three or seven consecutive days. The findings indicate that RF exposure leads to changes in adipose tissue markers, with some effects being dose-dependent and time-dependent. In brown adipose tissue (BAT), after 3 days of RF exposure, thermogenesis is reduced, mitochondrial activity in BAT decreases, and an increase in gene expression, responsible for balancing the regulatory and damaging effects of reactive oxygen species (ROS), was observed. This effect was partially compensated after 7 days of exposure. In white adipose tissue (WAT), RF exposure results in reduced fatty acid oxidation, impaired energy production, and hindered adipocyte differentiation. Notably, no effects of RF on mitochondrial biogenesis in WAT were observed. These findings contribute to understanding the effects of RF exposure on adipose tissue metabolism and thermoregulation, highlighting dose-dependent and time-dependent responses

Evaluation of permethrin disposition in pregnant rats and fetuses during in utero exposure using a physiological based pharmacokinetic (PBPK) model

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Approche intégrée in vitro pour étudier l’impact des pesticides sur l’axe microbiote-intestin-cerveau

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Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model

International audienceBiomonitoring studies have highlighted the exposure of pregnant women to pyrethroids based on the measurement of their metabolites in urine. Pyrethroids can cross the placental barrier and be distributed in the fetus as some pyrethroids were also measured in the meconium of newborns. Prenatal exposure to pyrethroids is suspected to alter the neurodevelopment of children, and animal studies have shown that early life exposure to permethrin, one of the most commonly used pyrethroid in household applications, can alter the brain development. This study aimed to characterize the fetal permethrin exposure throughout gestation in rats. We developed a pregnancy physiologically based pharmacokinetic (pPBPK) model that describes the maternal and fetal kinetics of the cis - and trans - isomers of permethrin during the whole gestation period. Pregnant Sprague–Dawley rats were exposed daily to permethrin (50 mg/kg) by oral route from the start of gestation to day 20. Permethrin isomers were quantified in the feces, kidney, mammary gland, fat, and placenta in dams and in both maternal and fetal blood, brain, and liver. Cis - and trans -permethrin were quantified in fetal blood and tissues, with higher concentrations for the cis -isomer. The pPBPK model was fitted to the toxicokinetic maternal and fetal data in a Bayesian framework. Several parameters were adjusted, such as hepatic clearances, partition coefficients, and intestinal absorption. Our work allowed to estimate the prenatal exposure to permethrin in rats, especially in the fetal brain, and to quantitatively estimate the placental transfer. These transfers could be extrapolated to humans and be incorporated in a human pPBPK model to estimate the fetal exposure to permethrin from biomonitoring data

L'exposition chronique péri-gestationnelle au chlorpyrifos ± au régime obésogène entraîne des perturbations du microbiote intestinal et des propriétés de la BHE chez les rats femelles et leur progéniture

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Determination of maternal and foetal distribution of cis- and trans-permethrin isomers and their metabolites in pregnant rats by liquid chromatography tandem mass spectrometry (LC-MS/MS)

We developed a method to quantify cis-permethrin and trans-permethrin and their metabolites in several biological matrices in pregnant rats and foetuses using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The objective was to quantify cis-permethrin and trans-permethrin in faeces, kidney, mammary gland, fat and placenta in mothers and in both maternal and foetal blood, brain and liver. The metabolites cis-3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis-DCCA), trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (trans-DCCA) and 3-phenoxybenzoic acid (3-PBA) were measured in blood, liver and urine. Sample preparation was performed by liquid-liquid extraction. A purification step was not carried out except for the more complex biological samples (fat, mammary glands and faeces). Validation parameters including specificity, linearity, matrix effect, limits of quantification (LOQs), accuracy and precision were evaluated. The recoveries of target compounds ranged from 47 to 136%. LOQs were in the range 4 to 80 ng/mL for permethrin isomers and 4 to 800 ng/mL for their respective metabolites. Intra- and inter-batch precision and accuracy in matrix were better than 15%. The validated method was applied in a preliminary toxicokinetic study in pregnant rats with oral dosing of 50 mg/kg permethrin. In pregnant rats, permethrin isomers and their metabolites were quantified in all requested matrices except maternal liver and blood for trans-permethrin and cis-DCCA respectively. In foetuses, cis- and trans-permethrin were also quantified, demonstrating that the method is suitable for the analysis of foetal distribution of permethrin in toxicokinetic studies

Combinaison de modèles in vivo et in vitro pour étudier la co-exposition des effets chroniques des pesticides et du régime obésogène en supplémentation d’un prébiotique (inuline) sur le microbiote intestinal et sur la barrière hémato-encéphalique chez des populations sensibles

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