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

The 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.

Impact of Perinatal Coexposure to Chlorpyrifos and a High-Fat Diet on Kisspeptin and GnRHR Presence and Reproductive Organs.

Emerging evidence has indicated the involvement of extrahypothalamic Kisspeptin and GnRHR in reproductive function. In this study, we evaluate if maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) has an impact on the expression of Kisspeptin and GnRHR in the reproductive organs of rats' offspring. A total of 16 pregnant rats are divided into four groups: a control group (n = 4), CPF group (4 rats exposed daily to 1/mg/kg/day), HFD group (4 rats randomly fed a 5.25 kcal/g HFD), and coexposed group (4 rats exposed to CPF and HDF). At postnatal development postnatal day (PND) 60, male and female offspring were sacrificed. The reproductive organs (ovary and testis) were removed, and histological and immunohistological analysis and in silico quantification (TissueGnostics software 6.0.1.102, TissueFAXS, HistoQuest) were applied to investigate the impact of different treatments on Kisspeptin and GnRHR expression in reproductive organs. The main outcomes of the study showed a significant decrease in rat offspring's body weight in the CPF group from PND30 and PND60 (p < 0.05 and p < 0.01, respectively). Histological analysis showed a significant increase in the atretic follicle and abnormal testis structure with germ cell desquamation in the CPF-exposed group. The immunodetection quantification of protein shows a significant decrease in GnRHR and Kisspeptin in the HFD and CPF exposed groups, respectively, in testis rat offspring. Perinatal exposure to CPF and HFD exposure affect the reproduction function of rat offspring.

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

Recent 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.

Perigestational exposure of a combination of a high-fat diet and pesticide impacts the metabolic and microbiotic status of dams and pups; a preventive strategy based on prebiotics.

PURPOSE: Metabolic changes during the perinatal period are known to promote obesity and type-2 diabetes in adulthood via perturbation of the microbiota. The risk factors for metabolic disorders include a high-fat diet (HFD) and exposure to pesticide residues. The objective of the present study was to evaluate the effects of perigestational exposure to a HFD and chlorpyrifos (CPF) on glycemia, lipid profiles, and microbial populations in Wistar dams and their female offspring. We also tested a preventive strategy based on treatment with the prebiotic inulin. METHODS: From 4 months before gestation to the end of the lactation period, six groups of dams were exposed to either a standard diet, a HFD alone, CPF alone, a combination of a HFD and CPF, and/or inulin supplementation. All female offspring were fed a standard diet from weaning to adulthood. We measured the impacts of these exposures on glycemia, the lipid profile, and the microbiota (composition, metabolite production, and translocation into tissues). RESULTS: HFD exposure and CPF + HFD co-exposure induced dysmetabolism and an imbalance in the gut flora in both the dams and the female offspring. Inulin mitigated the impact of exposure to a HFD alone but not that of CPF + HFD co-exposure. CONCLUSION: Our results provide a better understanding of the complex interactions between environmental pollutants and diet in early life, including in the context of metabolic diseases.

Chronic Perigestational Exposure to Chlorpyrifos Induces Perturbations in Gut Bacteria and Glucose and Lipid Markers in Female Rats and Their Offspring.

An increasing burden of evidence is pointing toward pesticides as risk factors for chronic disorders such as obesity and type 2 diabetes, leading to metabolic syndrome. Our objective was to assess the impact of chlorpyrifos (CPF) on metabolic and bacteriologic markers. Female rats were exposed before and during gestation and during lactation to CPF (1 mg/kg/day). Outcomes such as weight, glucose and lipid profiles, as well as disturbances in selected gut bacterial levels, were measured in both the dams (at the end of the lactation period) and in their female offspring at early adulthood (60 days of age). The results show that the weight of CPF dams were lower compared to the other groups, accompanied by an imbalance in blood glucose and lipid markers, and selected gut bacteria. Intra-uterine growth retardation, as well as metabolic disturbances and perturbation of selected gut bacteria, were also observed in their offspring, indicating both a direct effect on the dams and an indirect effect of CPF on the female offspring. Co-treatment with inulin (a prebiotic) prevented some of the outcomes of the pesticide. Further investigations could help better understand if those perturbations mimic or potentiate nutritional risk factors for metabolic syndrome through high fat diet.

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

Biomonitoring 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.

Perinatal exposure to chlorpyrifos and/or a high-fat diet is associated with liver damage in male rat offspring.

Metabolic impairments in childhood are known to promote the development of type 2 diabetes and/or obesity in adulthood. These impairments may result from perinatal exposure to harmful environmental factors, such as pesticide residues or the consumption of a "western" diet. In the present study, we sought to determine whether an obesogenic profile, metabolic disorders and liver damage in offspring (observed during young adulthood) were related to maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) starting 4 months before conception and ending at weaning. After the end of exposure, 51 male rat pups were left to develop under normal conditions and were studied in young adulthood. Despite the absence of direct exposure to harmful factors (other than through the dam's milk), maternal exposure to CPF or an HFD was associated with changes in the offspring's metabolic activity in the liver in the offspring. This indirect exposure to CPF was associated with a relative reduction in the expression of genes coding for enzymes involved in lipid or glucose metabolism but did induce histopathological changes in the offspring at adulthood. Maternal exposure to an HFD alone or to CPF alone gave similar results in offspring, changes in the same direction. Exposure of the mother to HFD did not exacerbate CPF effects. Co-exposure to both CPF and HFD did not increase the observed effects compared to each factor taken separately.

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.