International audience | On September 26th 2019, a major fire occurred in the Lubrizol factory located near the Seine estuary, in RouenFrance. Juvenile flounders were captured in the Canche estuary (a reference system) and caged one month in the Canche and in the Seine downstream the accident site. No significant increases of PAHs, PCBs and PFAS was detected in Seine vs Canche sediments after the accident, but a significant increase of dioxins and furans was observed in water and sewage sludge in the Rouen wastewater treatment plant. The proteomics approach highlighted a dysregulation of proteins associated with cholesterol synthesis and lipid metabolism, in fish caged in the Seine. The overall results suggested that the fire produced air borne dioxins and furans that got deposited on soil and subsequently entered in the Seine estuarine waters via runoff; thus contaminating fish preys and caged flounders in the Seine estuary.

Ractopamine, a synthetic β-adrenoreceptor agonist, is used as an animal feed additive to increase food conversion efficiency and accelerate lean mass accretion in farmed animals. The U.S. Food and Drug Administration claimed that ingesting products containing ractopamine residues at legal dosages might not cause short-term harm to human health. However, the effect of ractopamine on chronic inflammatory diseases and atherosclerosis is unclear. Therefore, we investigated the effects of ractopamine on atherosclerosis and its action mechanism in apolipoprotein E-null (apoe⁻/⁻) mice and human endothelial cells (ECs) and macrophages. Daily treatment with ractopamine for four weeks increased the body weight and the weight of brown adipose tissues and gastrocnemius muscles. However, it decreased the weight of white adipose tissues in apoe⁻/⁻ mice. Additionally, ractopamine exacerbated hyperlipidemia and systemic inflammation, deregulated aortic cholesterol metabolism and inflammation, and accelerated atherosclerosis. In ECs, ractopamine treatment induced endothelial dysfunction and increased monocyte adhesion and transmigration across ECs. In macrophages, ractopamine dysregulated cholesterol metabolism by increasing oxidized low-density lipoprotein (oxLDL) internalization and decreasing reverse cholesterol transporters, increasing oxLDL-induced lipid accumulation. Collectively, our findings revealed that ractopamine induces EC dysfunction and deregulated cholesterol metabolism of macrophages, which ultimately accelerates atherosclerosis progression.

Various microplastics (MPs) are found in the environment and organisms. MP residues in organisms can affect health; however, their impacts on metabolism in aquatic organisms remain unclear. In this study, zebrafish embryos were exposed to polyethylene MPs with sizes ranging from 1 to 4 μm at concentrations of 0, 10, 100, and 1000 μg/L for 7 days. Through qPCR technology, the results indicated that zebrafish exposed to polyethylene MPs exhibited significant change in microbes of the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia, etc. Moreover, 16S RNA gene sequencing revealed that there was a significant difference in alpha diversity between the control and 1000 μg/L MP-treated groups. At the genus level, the abundance of Aeromonas, Shewanella, Microbacterium, Nevskia and Methyloversatilis have increased remarkably. Conversely, the abundance of Pseudomonas, Ralstonia and Stenotrophomonas were significant reduction after MPs exposure. In addition, the levels of TG (triglyceride), TCHO (total cholesterol), NEFA (nonesterified fatty acid), TBA (total bile acid), GLU (glucose) and pyruvic acid significantly changed in MP-treated larval zebrafish, indicating that their metabolism was disturbed by MPs. Transcriptional levels of glucose and lipid metabolism-related genes showed a decreasing trend. Furthermore, LC/MS-based nontargeted metabolomics analysis demonstrated that a total of 59 phospholipid-related substances exhibited significant changes in larval fish treated with 1000 μg/L MPs. The mRNA levels of phospholipid metabolism-related genes were also obviously changed. Pearson correlation analysis indicated that the abundance of Aeromonas, Shewanella and Chitinibacter bacteria showed a negative correlation with most phospholipids, while Nevskia, Parvibacter and Lysobacter showed a positive correlation with most phospholipids. Based on these results, it is suggested that 1–4 μm PE-MPs could impact the microbiome and metabolism of larval zebrafish. All of these results indicated that the health risk of MPs cannot be ignored.

Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue.We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice.Pregnant C57BL6/J mice were exposed to BPS (1.5 μg/kg bw/day ie a human equivalent dose of 0.12 μg/kg bw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed.In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females.BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females.

Drilled seeds are an important food resource for many farmland birds but may pose a serious risk when treated with pesticides. Most compounds currently used as seed treatment in the EU have low acute toxicity but may still affect birds in a sub-chronic or chronic way, especially considering that the sowing season lasts several weeks or months, resulting in a long exposure period for birds. Tebuconazole is a triazole fungicide widely used in agriculture but its toxicity to birds remains largely unknown. Our aim was to test if a realistic scenario of exposure to tebuconazole treated seeds affected the survival and subsequent reproduction of the red-legged partridge (Alectoris rufa). We fed captive partridges with wheat seeds treated with 0%, 20% or 100% of tebuconazole application rate during 25 days in late winter (i.e. tebuconazole dietary doses were approximately 0.2 and 1.1 mg/kg bw/day). We studied treatment effects on the physiology (i.e. body weight, biochemistry, immunology, oxidative stress, coloration) and reproduction of partridges. Exposed birds did not reduce food consumption but presented reduced plasmatic concentrations of lipids (triglycerides at both exposure doses, cholesterol at high dose) and proteins (high dose). The coloration of the eye ring was also reduced in the low dose group. Exposure ended 60 days before the first egg was laid, but still affected reproductive output: hatching rate was reduced by 23% and brood size was 1.5 times smaller in the high dose group compared with controls. No significant reproductive effects were found in the low dose group. Our results point to the need to study the potential endocrine disruption mechanism of this fungicide with lagged effects on reproduction. Risk assessments for tebuconazole use as seed treatment should be revised in light of these reported effects on bird reproduction.

Both air pollution and dyslipidemias contributed to large number of deaths and disability-adjusted life lost years. Long-term air pollution exposure was related to changed blood lipids and risk of dyslipidemias. This study was designed to evaluate relationships between air pollutants, blood lipids and prevalence of dyslipidemias in a Chinese rural population exposed to high-level air pollution based on baseline data of The Henan Rural Cohort study. An amount of 39,057 participants from rural areas in China were included. The 3-year average exposure of air pollutants (PM2.5, PM10, NO2) was estimated by a spatiotemporal model. Logistic and linear regression models were employed to explore relationships between air pollutants, blood lipids (TC, TG, HDL-C and LDL-C) and prevalence of dyslipidemias. The three-year concentration of PM2.5, PM10 and NO2 was 72.8 ± 2.3 μg/m3, 131.5 ± 5.7 μg/m3and 39.1 ± 3.1 μg/m3, respectively. Overall, increased air pollution exposure was related to increased TC and LDL-C, while decreased TG and HDL-C. Each 1-μg/m3 increment of PM2.5 was related to 0.10% (0.07%–0.19%) increase in TC, 0.63% (0.50%–0.77%) increase in LDL-C, 2.93% (2.70%–3.16%) decrease in TG, 0.49% (0.38%–0.60%) decrease in HDL-C; and 5.7% (95%CI: 3.7%–7.6%), 4.0% (95%CI: 2.1%–6.0%) and 3.8% (95%CI: 2.5%–5.1%) increase in odds for hypercholesterolemia, hyperbetalipoproteinemia and hypoalphalipoproteinemia, respectively. Stronger associations were found in male and older participants. Findings suggest that air pollutants were associated with changed blood lipid levels and higher risk of dyslipidemias among rural population. Male and elder people should pay more attention to personal safety protection.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetically manufactured chemicals recognized to be toxic, bioaccumulative, and persistent. Previous studies on PFAS exposure and serum lipid levels have mainly focused on individual PFASs; however, the influence of multiple-PFAS exposure on the serum lipid profile remains unclear. This study was performed to evaluate the combined effects of multiple PFASs on serum lipid levels. Based on the National Health and Nutrition Examination Survey (NHANES) data (2011–2014), we first established a linear regression model to estimate the association between single-PFAS exposure and the serum lipid profile. Then, a weighted quantile sum (WQS) regression model and a Bayesian kernel machine regression (BKMR) model were used to evaluate the effects of multiple-PFAS exposure on the serum lipid profile. A mediating effect model was used to assess how albumin mediates these effects. We found that PFASs were significantly associated with the levels of serum lipids, including high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC). The WQS index was significantly correlated with the levels of HDL (β: 2.03, 95% CI: 0.74–3.32, P-value = 0.002), LDL (β: 4.16, 95% CI: 1.07–7.24, P-value = 0.008) and TC (β: 6.54, 95% CI: 3.00–10.1, P-value < 0.001). In the BKMR analysis, our results demonstrated that the effect of PFASs on serum lipids increased significantly when the concentrations of the PFASs were at their 60th percentiles or above compared to those at their 50th percentile. Mediation analysis showed that albumin mediated the effects of selected PFASs on the levels of serum lipids except for triglycerides (TG). PFAS exposure was correlated with the levels of serum lipids, and this correlation was mediated by albumin. Our results suggest that a comprehensive evaluation of multi-PFAS exposure could better characterize real-life exposure compared with single-PFAS exposure.

Because oil spills frequently occur in coastal regions that serve as spawning habitat, characterizing the effects of oil in estuarine fish carries both economic and environmental importance. There is a breadth of research investigating the effects of crude oil on fish, however few studies have addressed how transcriptional responses to oil change throughout development or how these responses might be conserved across taxa. To investigate these effects, we performed RNA-seq and pathway analysis following oil exposure 1) in a single estuarine species (Cyprinodon variegatus) at three developmental time points (embryos, yolk-sack larvae, free-feeding larvae), and 2) in two ecologically similar species (C. variegatus and Fundulus grandis), immediately post-hatch (yolk-sack stage). Our results indicate that C. variegatus embryos mount a diminished transcriptional response to oil compared to later stages, and that few transcriptional responses are conserved throughout development. Pathway analysis of larval C. variegatus revealed dysregulation of similar biological processes at later larval stages, including alteration of cholesterol biosynthesis pathways, cardiac development processes, and immune functions. Our cross-species comparison showed that F. grandis exhibited a reduced transcriptional response compared to C. variegatus. Pathway analysis revealed that the two species shared similar immune and cardiac responses, however pathways related to cholesterol biosynthesis exhibited a divergent response as they were activated in C. variegatus but inhibited in F. grandis. Our results suggest that examination of larval stages may provide a more sensitive estimate of oil-impacts than examination of embryos, and challenge assumptions that ecologically comparable species respond to oil similarly.

Exposure to endocrine disrupting chemicals during the first 1000 days of life may have long-lasting adverse effects on cardio-metabolic risk in later life. This study aimed to examine the associations between maternal prenatal Bisphenol A (BPA) exposure and child cardio-metabolic risk factors at age 2 years in a prospective cohort. During 2012–2013, 218 pregnant women were enrolled at late pregnancy from Shanghai, China. Urinary BPA concentration was measured in prenatal and child 2-year spot urine samples, and classified into high, medium and low tertiles. Child adiposity anthropometric measurements, random morning plasma glucose, serum insulin, and lipids (high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride), systolic (SBP) and diastolic blood pressure (DBP) were measured. Linear regression was used to evaluate the associations between prenatal BPA and each of the cardio-metabolic risk factors in boys and girls, respectively, adjusting for pertinent prenatal, perinatal and postnatal factors. BPA was detectable (>0.1 μg/L) in 98.2% of mothers prenatally and 99.4% of children at age 2 years. Compared to those with low prenatal BPA, mean SBP was 7.0 (95%CI: 2.9–11.2) mmHg higher, and DBP was 4.4 (95%CI: 1.2–7.5) mmHg higher in girls with high prenatal BPA levels, but these associations were not found in boys. In boys, medium maternal prenatal BPA level was associated with 0.36 (95% CI: 0.04–0.68) mmol/L higher plasma glucose. No associations were found between prenatal BPA and child BMI, skinfold thicknesses, serum lipids, or insulin in either girls or boys. There were no associations between concurrent child urinary BPA and cardio-metabolic risk factors. These results support that BPA exposure during prenatal period, susceptible time for fetal development, may be associated with increase in child BP and plasma glucose in a sex-specific manner. Further independent cohort studies are needed to confirm the findings.

Pyrazole derivatives display diverse biological and pharmacological activities. The aim of this study is to investigate the antioxidant properties of a novel pyrazolecarboxamide derivative (4-amino-N-[(4-chlorophenyl)]-3-methyl-1-phenyl-1H-thieno [2, 3-c] pyrazole-5-carboxamide) in African catfish, Clarias gariepinus, exposed to 1 mg/L PbNO₃. Fish were intramuscularly injected with pyrazole-5-carboxamidederivative according to the following groupings: Group 1 (control), Group 2 (1 mg/L lead nitrate), Group 3 (1 mg/L lead nitrate + 5 mg pyrazole derivative/kg body weight), and Group 4 (1 mg/L lead nitrate + 10 mg pyrazole derivative/kg body weight) for two weeks and four weeks. Lead nitrate (1 mg/L) caused significant elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, uric acid, cholesterol, and glucose-6-phosphate dehydrogenase (G6PDH) compared to the control group after two and four weeks of exposure, while serum total lipids, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly reduced compared to the control group. Furthermore, levels of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and total antioxidant capacity (TAC) were reduced in group 2 compared to the control group. However, in group 2, hepatic lipid peroxidation (LPO) and DNA fragmentation percentage were significantly increased compared to the control group. Histopathological changes in the liver of lead-exposed groups included marked disturbance of hepatic tissue organization, degeneration of hepatocytes, dilation of blood sinusoids and the central vein as well as necrosis. Injection of pyrazole derivative for two weeks and four weeks reversed alterations in biochemical parameters, antioxidant biomarkers, lipid peroxidation, hepatic DNA damage, and histopathological changes in liver tissue induced by 1 mg/L lead nitrate. This amelioration was higher in response to high-dose pyrazole derivative (10 mg) at the fourth week of exposure, showing concentration-and time-dependency. Overall, the sensitized derivative pyrazolecarboxamide is likely a useful tool to minimize the effects of lead toxicity due to its potent antioxidant activity.