Publications by authors named "Yuanxiang Jin"

125 Publications

Bisphenol A impairs cognitive function and 5-HT metabolism in adult male mice by modulating the microbiota-gut-brain axis.

Chemosphere 2021 May 26;282:130952. Epub 2021 May 26.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, China. Electronic address:

Bisphenol A (BPA) has been found to promote hepatotoxicity, reproductive toxicity, and developmental toxicity. However, the neurotoxicity and mechanism of BPA on cognitive function are still unclear. To that end, eight-week-old adult male and female C57BL/6J mice were exposed to 0.05, 0.5, 5, and 50 mg/kg BPA by dietary supplementation for 22 weeks. BPA exposure impaired learning and memory in male mice, associated with increased neuroinflammation and damaged blood-brain barrier. BPA exposure reduced the tight junctions in the colon, resulting in dysfunction of the gut barrier. The levels of neurotransmitters in the serum, hippocampus, and colon of male mice, including tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, were all decreased by BPA, together with reduced expression of tryptophan and 5-HT metabolism-related genes. Cecal microbiota analysis revealed that the diversity and composition of the microbiota in male mice were markedly altered by BPA, leading to functional profile changes in the microbial community. These results suggest that the neurotoxicity of BPA in male mice may be partly regulated by the interactions of the microbiota-gut-brain axis. However, BPA has little effect on the cognitive function in female mice, which might be caused by the microbial differences and the role of estrogen receptors.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130952DOI Listing
May 2021

Embryonic toxicity of epoxiconazole exposure to the early life stage of zebrafish.

Sci Total Environ 2021 Jul 16;778:146407. Epub 2021 Mar 16.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Epoxiconazole (EPX), as a broad-spectrum triazole fungicide, is widely used in agriculture to resist pests and diseases, while it may have potential toxicity to non-target organisms. In the present study, early developmental stage zebrafish were used as the subject organisms to assess the toxicity of EPX, and the possible mechanism of toxicity was also discussed by biochemical and transcriptomic analysis. Through embryo toxicity test, we had made it clear that the 96 h LC of embryo was 7.204 mg/L, and acute exposure to EPX effected hatching rate, heartbeats, body length and even morphological defects. Then, by being exposed to EPX for 7 days at concentrations of 175 (1/40 LC), 350 (1/20 LC) and 700 (1/10 LC), biochemical parameters were affected, mainly manifested as increase of the triglyceride (TG) level and decrease of glucose content. Correspondingly, the transcription of genes related of glucose metabolism, lipid metabolism and cholesterol metabolism were also affected significantly in larval zebrafish. Moreover, some pathways, including lipid metabolism, glucose metabolism and amino acid metabolism were affected through transcriptome sequencing analysis in the larval zebrafish. Further data analysis based on the sequencing, EPX exposure also affected the expression of genes related to cell apoptosis. We further conformed that the bright fluorescence on the liver and bright spots near the liver by acridine orange staining. In addition, the mRNA levels of apoptosis related genes were also significantly affected in the EPX exposed larval zebrafish. Taken together, the work could provide an insight into toxic effects of EPX on the zebrafish larvae at embryo toxicity and transcriptional levels, providing some evidences for the toxic effects of triazole fungicides on non-target organisms.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146407DOI Listing
July 2021

6:2 Cl-PFESA has the potential to cause liver damage and induce lipid metabolism disorders in female mice through the action of PPAR-γ.

Environ Pollut 2021 May 10;287:117329. Epub 2021 May 10.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

6:2 Cl-PFESA is a polyfluoroalkyl ether with high environmental persistence that has been confirmed to have significant adverse effects on animals. In this study, 6-week-old female C57BL/6 mice were exposed to 0, 1, 3 and 10 μg/L 6:2 Cl-PFESA for 10 weeks to estimate the hepatotoxicity of 6:2 Cl-PFESA and explore its underlying molecular mechanism. The results indicated that 6:2 Cl-PFESA preferentially bioaccumulated in the liver and induced hepatic cytoplasmic vacuolation and hepatomegaly in mice. In addition, serum metabolic profiling showed that 6:2 Cl-PFESA exposure caused an abnormal increase in amino acids and an abnormal decrease in acyl-carnitine, which interfered with fatty acid transport and increased the risk of metabolic diseases. Further experiments showed that 6:2 Cl-PFESA formed more hydrogen bonds with PPAR-γ than PFOS, Rosi and GW9662, and the binding affinity of 6:2 Cl-PFESA toward PPAR-γ was the highest among the ligands. 6:2 Cl-PFESA promoted the differentiation of 3T3-L1 cells by increasing PPAR-γ expression. Therefore, our results showed that 6:2 Cl-PFESA has the potential to induce liver damage and dysfunction in female mice, and this effect was achieved through PPAR-γ. This study is the first to reveal the hepatic toxicity of 6:2 Cl-PFESA in female mammals and provides new insights for subsequent in-depth research.
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http://dx.doi.org/10.1016/j.envpol.2021.117329DOI Listing
May 2021

Developmental toxicity of procymidone to larval zebrafish based on physiological and transcriptomic analysis.

Comp Biochem Physiol C Toxicol Pharmacol 2021 May 15;248:109081. Epub 2021 May 15.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

As a broad-spectrum with low toxicity, procymidone (PCM), is widely used in agriculture and frequently observed in aquatic system, which may cause some impacts on aquatic organisms. Here, to determine the developmental toxicity of PCM, embryonic and larval zebrafish were exposed to PCM at 0, 1, 10, 100 μg/L in dehydrogenated natural water containing 0.01% acetone for 7 days. The results showed that high concentration of PCM could cause the pericardial edema and increase the heart rates in larval zebrafish, suggesting that PCM had developmental toxicity to zebrafish. We also observed that PCM exposure not only changed the physiological parameters including TBA, GLU and pyruvic acid, but also changed the transcriptional levels of glycolipid metabolism related genes. In addition, after transcriptomics analysis, a total of 1065 differentially expressed genes, including 456 up-regulated genes and 609 down-regulated genes, changed significantly in 100 μg/L PCM treated larval zebrafish. Interestingly, after GO (Gene Ontology) analysis, the different expression genes (DEGs) were mainly enriched to the three different biology processes including GABA-nervous, lipid Metabolism and response to drug. We also observed that the levels of GABA receptor related genes including gabrg2, gabbr1α, gabbr1 and gabra6α were inhibited by PCM exposure. Interestingly, the swimming distance of larval zebrafish had the tendency to decrease after PCM exposure, indicating that the nervous system was affected by PCM. Taken together, the results confirmed that the fungicide PCM could cause developmental toxicity by influencing the lipid metabolism and GABA mediated nervous system and behavior in larval zebrafish. We believed that the results could provide an important data for the influence of PCM on aquatic animals.
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http://dx.doi.org/10.1016/j.cbpc.2021.109081DOI Listing
May 2021

Maternal exposure of mice to sodium p-perfluorous nonenoxybenzene sulfonate causes endocrine disruption in both dams and offspring.

Endocr J 2021 May 11. Epub 2021 May 11.

Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

The toxicity of certain novel perfluoroalkyl substances (PFCs) has attracted increasing attention. However, the toxic effects of sodium p-perfluorous nonenoxybenzene sulfonate (OBS) on the endocrine system have not been elucidated. In this study, OBS was added to the drinking water during the pregnancy and lactation of the healthy female mice at dietary levels of 0.0 mg/L (CON), 0.5 mg/L (OBS-L), and 5.0 mg/L (OBS-H). OBS exposure during the pregnancy and lactation resulted in the presence of OBS residues in the placenta and fetus. We also analyzed physiological and biochemical parameters and gene expression levels in mice of the F0 and F1 generations after maternal OBS exposure. The total serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly increased in female mice of the F0 generation. The androgen levels in the serum and the ovarian mRNA levels of androgen receptor (AR) also tended to increase after maternal OBS exposure in the F0 generation mice. Moreover, maternal OBS exposure altered the mRNA expression of endocrine-related genes in male mice of F1 generation. Notably, the serum TC and LDL-C levels were significantly increased in 8-weeks-old male mice of the F1 generation, and the serum high-density lipoprotein cholesterol (HDL-C) levels were decreased in 24-week-old male mice of the F1 generation. These results indicated that maternal OBS exposure can interfere with endocrine homeostasis in the F0 and F1 generations. Therefore, exposure to OBS during pregnancy and lactation has the potential toxic effects on the dams and male offspring, which cannot be overlooked.
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http://dx.doi.org/10.1507/endocrj.EJ20-0781DOI Listing
May 2021

Microplastic: A potential threat to human and animal health by interfering with the intestinal barrier function and changing the intestinal microenvironment.

Sci Total Environ 2021 Sep 27;785:147365. Epub 2021 Apr 27.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Plastics are widely used in many fields due to their stable physical and chemical properties, and their global production and usage increase significantly every year, which leads to the accumulation of microplastics in the entire ecosystem. Numerous studies have shown that microplastics (MPs) have harmful effects on living organisms. This review aims to provide a comprehensive conclusion of the current knowledge of the impacts of MPs on the stability of the gut microenvironment, especially on the gut barrier. Studies showed that exposure to MPs could cause oxidative damage and inflammation in the gut, as well as the destruction of the gut epithelium, reduction of the mucus layer, microbial disorders, and immune cell toxicity. Although there are few reports directly related to humans, we hoped that this review could bring together more and more evidence that exposure to MPs results in disturbances of the intestinal microenvironment. Therefore, it is necessary to investigate their threats to human health further.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147365DOI Listing
September 2021

Combined hepatotoxicity of imidacloprid and microplastics in adult zebrafish: Endpoints at gene transcription.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Aug 16;246:109043. Epub 2021 Apr 16.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Microplastics (MPs) and pesticides are two kinds of ubiquitous pollutants that can pose a health risk to aquatic organisms. However, researches about the combined effects of MPs and pesticides are very limited. A simple combined exposure model was established in this study, adult zebrafish were exposed to 100 μg/L imidacloprid (IMI), 20 μg/L polystyrene microplastics (PS), and a combination of PS and IMI (PS + IMI) for 21 days. The results demonstrated that exposure to PS and IMI inhibited the growth of zebrafish and altered the levels of glycolipid metabolism and oxidative stress-related biochemical parameters. While gene expression analysis revealed that, compared with PS or IMI treatment group, combined exposure caused a greater change in gene expression levels involving the process of glycolipid metabolism (Gk, Hk1, Aco, PPar-α, Cpt1, Acc, Fas, PPar-γ, Apo) and inflammatory response (IL-1β, IL-6, IL-8, TNF-α, IL-10). The results demonstrated that even combined exposure of low concentrations of PS and IMI could cause more severe hepatotoxicity in zebrafish, especially in terms of gene transcription. And more combined toxicity studies are essential for MPs and pesticides risk assessment.
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http://dx.doi.org/10.1016/j.cbpc.2021.109043DOI Listing
August 2021

Effects of polyethylene microplastics on the microbiome and metabolism in larval zebrafish.

Environ Pollut 2021 Aug 31;282:117039. Epub 2021 Mar 31.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.envpol.2021.117039DOI Listing
August 2021

Low concentrations of imidacloprid exposure induced gut toxicity in adult zebrafish (Danio rerio).

Comp Biochem Physiol C Toxicol Pharmacol 2021 Mar 6;241:108972. Epub 2021 Jan 6.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Neonicotinoid insecticide imidacloprid (IMI) is widely used in agriculture, and its repeated application may result in environmental pollution. Recently, the toxicity of IMI to non-target animals has received increasing attention. In the current study, adult zebrafish were exposed to low concentrations of IMI (100 and 1000 μg/L) for 21 days. The results showed that IMI exposure induced intestinal histological injury and oxidative stress in the gut of zebrafish, and the levels of superoxide dismutase (SOD), catalase (CAT) were noticeably increased. Furthermore, IMI exposure also resulted in higher intestinal LPS levels and significant increases in the expression of inflammatory factors. Simultaneously, IMI exposure also slightly induced gut microbiota dysbiosis and specific bacteria alterations. These findings indicated that low concentrations of IMI could induce gut toxicity in adult zebrafish, which could provide new insights into the potential risks of IMI to aquatic animals.
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http://dx.doi.org/10.1016/j.cbpc.2020.108972DOI Listing
March 2021

Polystyrene nanoparticles trigger the activation of p38 MAPK and apoptosis via inducing oxidative stress in zebrafish and macrophage cells.

Environ Pollut 2021 Jan 1;269:116075. Epub 2020 Dec 1.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Polystyrene nanoparticles (PS NPs), originated from breakdown of large plastic wastes, have already caused much concern for their environmental risks on health. This current study was aimed to reveal the toxicological mechanism of PS NPs on developing zebrafish and macrophage cells. To fulfill this purpose, 42 nm PS NPs were exposed to the early development stage of zebrafish for 5 days, the decreased heart rate and locomotor activity of zebrafish larvae were observed. The fluorescent PS NPs were used to precisely assess the accumulation of PS NPs in zebrafish larvae, and the results indicated that PS NPs not only accumulated in digestive system, but also infiltrated into the liver. More importantly, the transcriptomic analysis revealed that a total of 356 genes were differentially expressed and the KEGG class map showed significant differences in the MAPK pathway upon PS NPs treatment. Meanwhile, the induction of oxidative stress and inflammation were also observed in zebrafish larvae. Furthermore, PS NPs also induced oxidative damage and inflammatory response in RAW 264.7 cells, which activated p38 MAPK signal pathway and finally induced cell apoptosis. Our study provides a new understanding of MAPK signaling pathway involved in toxicity mechanism.
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http://dx.doi.org/10.1016/j.envpol.2020.116075DOI Listing
January 2021

Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials.

BMC Pharmacol Toxicol 2020 12 4;21(1):86. Epub 2020 Dec 4.

Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China.

Background: Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other lipid-lowering drugs is better than these drugs alone. This study systematically reviewed the efficacy and safety of bempedoic acid monotherapy or combination togethers in hypercholesterolemic patients.

Methods: Randomized controlled trials were searched across Medline, Embase, Cochrane library, web of science, etc. The net change scores [least squares mean (LSM) percentage change] in LDL-C level were meta-analyzed using weighted mean difference. The reductions in other lipids including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein (ApoB) and high sensitivity C reactive protein (hsCRP) were also assessed. Odds ratio (OR) of the incidence of adverse events (AEs) were calculated to evaluate the safety of bempedoic acid.

Results: A total of 13 trials (4858 participates) were included. Pooled data showed that the combination togethers resulted in greater reductions in LDL-C level than monotherapies (bempedoic acid + statin vs. statin: LSM difference (%), - 18.37, 95% CI, - 20.16 to - 16.57, I = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), - 18.89, 95% CI, - 29.66 to - 8.13, I = 87%). But the difference in efficacy between bempedoic acid and ezetimibe was not obvious. Meta-regression analysis showed the treatment duration was a source of heterogeneity (adj R = 16.92, 95% CI, 0.04 to 0.72). Furthermore, the background therapy of statin before screening decreased the efficacy of bempedoic acid. In addition, bempedoic acid also resulted in a significant reduction in TC, non-HDL-C, ApoB and hsCRP level. The OR of muscle-related AEs by the combination of bempedoic acid and statin was 1.29 (95% CI, 1.00 to 1.67, I = 0) when compared with statin alone.

Conclusion: This study showed the efficacy of combination togethers were similar but stronger than these drugs alone. Of note, a trend of high risk of muscle-related AEs by the combination of bempedoic acid and statin was observed, though it is not statistically significant, such risk is needed to be confirmed by more trials, because it is important for us to determine which is the better combinative administration for statin-intolerant patients.
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http://dx.doi.org/10.1186/s40360-020-00463-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716459PMC
December 2020

Effects of chlorothalonil, prochloraz and the combination on intestinal barrier function and glucolipid metabolism in the liver of mice.

J Hazard Mater 2021 05 21;410:124639. Epub 2020 Nov 21.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Chlorothalonil (CHL) and procymidone (PRO) are fungicides that exhibit low toxicity and are widely used in many countries. And both fungicides are frequently detected in the food chain. However, the health risk posed by these fungicides is still unclear. Here, 8-week-old male C57BL/6 mice were orally treated with CHL (10, 50 mg/kg/day), PRO (20, 100 mg/kg/day) and CHL+PRO (5+10, 25+50 mg/kg/day) by dietary supplementation for 10 weeks. Hepatic pathological analysis showed that exposure to CHL, PRO and CHL+PRO could cause liver injury. The glucose, triglyceride (TG) levels and the related gene expression to glucolipid metabolism changed significantly. The significantly reduced acylcarnitine levels demonstrated that CHL, PRO and CHL+PRO exposure inhibited fatty acids (FAs) β-oxidation. In addition, CHL and PRO altered the structure of the gut microbiota and destroyed the integrity of the intestinal barrier function. In particular, AF12, Odoribacter, Prevotella and Lactobacillus were highly correlated with carnitine. The results showed that CHL, PRO and CHL+PRO exposure might inhibit FAs β-oxidation by decreasing cystic fibrosis transmembrane conductance regulator (CFTR)-mediated ion transport, indicating that these fungicides disturbed intestinal barrier function associated with glucolipid metabolism disorder. Here, the data also indicated that there was an additive effect between CHL and PRO in mice.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124639DOI Listing
May 2021

Health risks of chlorothalonil, carbendazim, prochloraz, their binary and ternary mixtures on embryonic and larval zebrafish based on metabolomics analysis.

J Hazard Mater 2021 02 10;404(Pt B):124240. Epub 2020 Oct 10.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Chlorothalonil (CTL), carbendazim (CBZ), and prochloraz (PCZ) are fungicides widely used in many countries. The use of these fungicides raises concerns because they are often applied together or used in the same agricultural area. However, the toxicity of these fungicides or mixtures, especially to aquatic organisms, has received limited attention. Here, embryonic and larval zebrafish were exposed to indicated concentrations of CTL, CBZ, and PCZ and their binary (CTL+CBZ, CTL+PCZ and CBZ+PCZ) and ternary (CTL+CBZ+PCZ) mixtures for 24 h. Based on metabolomics analysis, we observed that hundreds of metabolites were altered, and glycolysis metabolism and amino acid metabolism were the two most affected pathways. Interestingly, a total of 9 and 26 metabolites changed significantly in embryos and larvae treated with all fungicides, respectively. Among these altered metabolites, 2-aminoadipic acid (2-AAA) levels increased significantly in all groups, indicating that 2-AAA potentially represents a useful biomarker for evaluating the toxicity of fungicides. Furthermore, the joint effects of CTL+PCZ on embryos and larvae, especially on amino acid metabolism, were weaker than those in other groups, but combined treatment did not influence individual fungicidal activity. Data acquired from metabolomics provided important insight for understanding the mechanism by which fungicides or their mixtures affect zebrafish.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124240DOI Listing
February 2021

Maternal exposure to imazalil disrupts intestinal barrier and bile acids enterohepatic circulation tightly related IL-22 expression in F, F and F generations of mice.

J Hazard Mater 2021 02 9;403:123668. Epub 2020 Aug 9.

Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

There is a growing body of evidence linking maternal exposure of environmental pollutants to intestinal and metabolic diseases that can be conserved across multiple generations. Here, female C57BL/6 mice were treated imazalil (IMZ) at dietary levels of 0, 0.025‰ and 0.25‰ during the gestation and lactation periods. The results demonstrated that IMZ treatment not only induced significant changes in the mucus secretion and ionic transport, but also disrupted the expression of antimicrobial peptides in the intestine of F, F and F generations. In addition, IMZ exposure altered BAs metabolism and the affected the expression levels of critical genes involved in BAs synthesis, signaling, transportation and apical uptake. The immune cell-produced cytokines were displaying extraordinary changes after IMZ exposure. In particular, whether it was in F0, F1-20d, F1-7 w or F2-20d, the expression of IL-22 had the trend of markedly increasing upon IMZ exposure. Correlation analyses revealed that the expression of IL-22 was positively correlated with the change of BAs metabolites. Together, all these results indicated that IMZ exposure was perceived as a major stress by the intestinal epithelium that strongly affected the intestinal barrier function (including mucus, CFTR, AMPs, inflammation), largely in response to an alteration of BAs metabolism.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123668DOI Listing
February 2021

Imidacloprid disturbed the gut barrier function and interfered with bile acids metabolism in mice.

Environ Pollut 2020 Nov 8;266(Pt 1):115290. Epub 2020 Aug 8.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, Zhejiang, China. Electronic address:

The toxicity of neonicotinoid insecticide imidacloprid (IMI) to mammals has recently received increasing attention. However, the effects of IMI on the gut barrier and liver function of male C57BL/6J mice are still unknown. The study showed that exposure to IMI could reduce relative liver weights, change hepatic tissue morphology and induce hepatic oxidative stress. The gut barrier function was greatly impaired by IMI exposure, which might increase the body's susceptibility to harmful substances in the gut. Meanwhile, the synthesis and metabolism of hepatic bile acids (BAs) was also affected by IMI exposure. The levels of serum and hepatic total bile acids (TBAs) decreased; in contrast, the fecal TBA levels increased after exposure to 30 mg/L IMI for 10 weeks. Sequencing of colonic contents revealed that the operational taxonomic units (OTUs) and α-diversity index increased and that the gram-negative bacteria overgrew, indicating that the balance of the gut microbiota was disrupted. The present study indicated that subchronic exposure to IMI interfered with the gut barrier function, interfering with BAs metabolism and causing gut microbiota imbalance in male C57BL/6J mice. Taken together, IMI residues appear to be potentially toxic to mammals and even humans.
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http://dx.doi.org/10.1016/j.envpol.2020.115290DOI Listing
November 2020

β -Cypermethrin promotes the adipogenesis of 3T3-L1 cells via inducing autophagy and shaping an adipogenesis-friendly microenvironment.

Acta Biochim Biophys Sin (Shanghai) 2020 Aug;52(8):821-831

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

The toxicity of synthetic pyrethroids has garnered attention, and studies have revealed that pyrethroids promote fat accumulation and lead to obesity in mice. Nevertheless, the effect of β-cypermethrin (β-CYP) on adipogenesis and its underlying mechanism remains largely unknown. In this study, mouse embryo fibroblasts 3T3-L1 cells were exposed to β-CYP, and the cell viability, intracellular reactive oxygen species (ROS) level, autophagy, and adipogenesis were assessed to investigate the roles of oxidative stress and autophagy in the toxic effects of β-CYP on adipogenesis. The results demonstrated that treatment with 100 μΜ β-CYP elevated the ROS level, decreased mitochondrion membrane potential, stimulated autophagy, and enhanced the adipogenesis induced by the mixture of insulin, dexamethasone, and 3-isobutyl-1-methylxanthine. However, co-treatment with N-acetyl-L-cysteine partially blocked the abovementioned effects of β-CYP in 3T3-L1 cells. In addition, co-treatment with rapamycin, an autophagy agonist, enhanced the inductive effect of β-CYP on adipogenesis, whereas co-treatment with 3-methyladenine blocked the enhancement of adipogenesis caused by β-CYP. Moreover, β-CYP also altered the microenvironment of 3T3-L1 cells to an adipogenesis-friendly one by reducing the extracellular expression of miR-34a, suggesting that the culture media of β-CYP-treated 3T3-L1 cells could shift macrophages to M2 type. Taken together, the data obtained in the present study demonstrated that β-CYP promoted adipogenesis via oxidative stress-mediated autophagy disturbance, and it caused macrophage M2 polarization via the alteration of miR-34a level in the microenvironment. The study demonstrated the adipogenesis-promoting effect of β-CYP and unveiled the potential mechanism.
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http://dx.doi.org/10.1093/abbs/gmaa049DOI Listing
August 2020

Sub-chronic carbendazim exposure induces hepatic glycolipid metabolism disorder accompanied by gut microbiota dysbiosis in adult zebrafish (Daino rerio).

Sci Total Environ 2020 Oct 9;739:140081. Epub 2020 Jun 9.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Carbendazim (CBZ) as a broad spectrum fungicide is widely used in the whole world to contorl plant diseases. With the application of CBZ in the agriculture, it has been detected in vegetables and fruits. Nowadays, it even has been detected in the watercourse and indoor dust. However, the toxic effects of CBZ on aquatic organisms have received limited attention. In this study, male adult zebrafish were exposed at 0, 30 and 100 μg/L CBZ for 21 days to assess its effects on hepatic glycolipid metabolism. After exposure, the body weight and length decreased, but the condition factor increased significantly. Some hepatic biochemical parameters including the levels of glucose, pyruvate, low density lipoprotein (LDL) and triglyceride (TG) decreased significantly in the liver of zebrafish after exposure with CBZ. Two transaminases alanine transaminase (ALT) and aspartate transaminase (AST) also increased significantly, indicating that subchronic CBZ exposure influenced the liver function. Moreover, the relative mRNA levels of some key genes related to the glycolysis and lipid metabolism in the liver also changed significantly. Furthermore, the transcriptome analysis showed that the carbon metabolism, lipid metabolism and detoxification metabolism were also affected in the liver of CBZ exposed zebrafish. Interestingly, we also found the amounts of the Firmicutes, Bacteroidetes, Actinobacteria, α-Proteobacteria, γ-Proteobacteria and Verrucomicrobia at phylum level significantly decreased in the gut. Sequencing V3-V4 region of 16S rRNA also demonstrated gut microbiota composition changed significantly according to weighted UniFrac distance analysis. Consequently, subchronic CBZ exposure induced hepatic metabolic disorder accompanied by gut microbiota dysbiosis in adult male zebrafish.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140081DOI Listing
October 2020

Differential responses of larval zebrafish to the fungicide propamocarb: Endpoints at development, locomotor behavior and oxidative stress.

Sci Total Environ 2020 Aug 7;731:139136. Epub 2020 May 7.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

The fungicide propamocarb (PM) is widely used to protect cucumbers, tomatoes and other plants from pathogens. According to previous studies, PM could be detected in the aquatic system in some area. However, the toxic effects of PM on zebrafish received very limited attention. In this study, we examined the toxic effects of various concentration of PM on the endpoints of development, locomotor behavior and oxidative stress in larval zebrafish. It was observed that PM exposure delayed embryonic development, inhibited hatchability at 60 and 72 h postfertilization and increased heart rate. After PM exposure, the larval zebrafish showed abnormal free swimming behavior and the swimming behavior in response to light-dark transition, indicating that PM had the potential to induce neurotoxicity. Moreover, PM exposure also affected the enzymatic activity of acetylcholinesterase and dopamine and the transcriptional level of genes related to neurotoxicity. In addition, PM exposure not only affects catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activity but also affects the transcription level of various genes. We believed that PM induced oxidative stress was also a possible reason to cause neurotoxicity in larval zebrafish. In summary, our results suggested that PM could disturb the endpoints at development, locomotor behavior and oxidative stress in larval zebrafish.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139136DOI Listing
August 2020

Polystyrene microplastics decrease F-53B bioaccumulation but induce inflammatory stress in larval zebrafish.

Chemosphere 2020 Sep 11;255:127040. Epub 2020 May 11.

Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang, 330012, China. Electronic address:

There is growing concern that microplastics (MPs), which act as carriers of other organic contaminants, are mistakenly ingested by aquatic organisms, consequently causing unpredictable adverse effects. In this study, zebrafish larvae (6 d post fertilization) were exposed to either 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), polystyrene microplastics (PS-MPs) or their combination for 7 d to evaluate the effects of the presence of PS-MPs on the bioaccumulation and immunomodulation of F-53B. PS-MPs greatly promoted the sorption of F-53B, which reduced the bioavailability and bioaccumulation of F-53B in zebrafish larvae. F-53B, PS-MPs, or their mixture significantly reduced the body weight of zebrafish larvae. Combined exposure of PS-MPs and F-53B resulted in a significant reduction in superoxide dismutase (SOD) and lysozyme activity, indicating the occurrence of oxidative stress and inflammatory response in zebrafish larvae. The content of malondialdehyde (MDA) and immunoglobulin M (IgM) was not affected by F-53B or PS-MPs, but significantly increased in their combined exposure. Furthermore, co-exposure of F-53B and PS-MPs significantly upregulated the transcripts of pro-inflammatory cxcl-clc and il-1β genes and increased the levels of iNOS protein in zebrafish larvae. In addition, enhanced protein expression of NF-κB paralleled the upregulation in the expression of most immune-related genes, suggesting NF-κB pathway was mechanistically involved in these responses. Collectively, the presence of MPs decreased F-53B bioaccumulation, but induced inflammatory stress in larval zebrafish. These findings highlight the health risks of co-contamination of MPs and F-53B in aquatic environments.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127040DOI Listing
September 2020

Pesticides-induced energy metabolic disorders.

Sci Total Environ 2020 Aug 28;729:139033. Epub 2020 Apr 28.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Metabolic disorders have become a heavy burden on society. Recently, through excessive use, pesticides have been found to be present in environmental matrixes and sometimes even accumulate in humans or other mammals through the food chain, which then causes health concerns. Evidence has indicated that pesticides have the potential to induce energy metabolic disorders by disturbing the physical process of energy absorption in the intestine and energy storage in the liver, adipose tissue and skeletal muscle in humans or other mammals. In addition, the homeostasis of energy regulation by the pancreas and immune cells is also affected by pesticides. These pesticide-induced disruptions ultimately cause abnormal levels of blood glucose and lipids, which in turn induce the development of related metabolic diseases, including overweight, underweight, insulin resistance and even diabetes. In this review, the results of previous studies focused on the induction of metabolic disorders by pesticides are summarized. We hope that this work will facilitate the discovery of a potential strategy for the treatment of diseases caused by pesticides.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139033DOI Listing
August 2020

3-Methylcholanthrene alters the hepatic immune response in mice.

Acta Biochim Biophys Sin (Shanghai) 2020 05;52(5):570-572

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

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http://dx.doi.org/10.1093/abbs/gmaa020DOI Listing
May 2020

β-Cypermethrin Alleviated the Inhibitory Effect of Medium from RAW 264.7 Cells on 3T3-L1 Cell Maturation into Adipocytes.

Lipids 2020 05 31;55(3):251-260. Epub 2020 Mar 31.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China.

Studies have elucidated that pyrethroids induce adipogenesis. It is also known that macrophages can affect the homeostasis of adipose tissue. However, whether and how the β-cypermethrin (β-CYP)-mediated inhibition of the macrophages affects adipogenesis remain unknown. To explore the effects of β-CYP on adipogenesis through modulating the function of macrophages, 3T3-L1 cells, a preadipocyte cell line, were exposed to culture medium from either RAW 264.7 cells, a macrophage cell line (RM), or β-CYP-treated RAW 264.7 cells (CRM). CRM decreased the inhibitory effects of RM treatment on cell proliferation and adipogenesis, as lipid accumulation, the CEBPA content, and Fasn and Acaca expression in 3T3-L1 cells were higher following CRM treatment than following RM treatment through the higher levels of the demethylated CEBPA promoter in 3T3-L1 cells. However, the medium from β-CYP- and N-acetyl-L-cysteine-cotreated RAW 264.7 cells (CNRM) partially restored the inhibitory effects of RAW 264.7 cells on 3T3-L1 cells that had been reduced by CRM, indicating that β-CYP might reduce the cytotoxicity and inhibitory effects of RAW 264.7 cells on the adipogenesis of 3T3-L1 cells through elevating ROS levels in RAW 264.7 cells. Moreover, exposure to β-CYP downregulated the TNF-α secretion in RAW 264.7 cells. In conclusion, these data demonstrated that β-CYP affected the function of RAW 264.7 cells, alleviating their inhibitory effects on adipogenesis and CEBPA demethylation in 3T3-L1 cells. β-CYP might achieve these effects through downregulating the secretion of TNF-α via elevating ROS levels in RAW 264.7 cells. Our experiments provide a new perspective on the obesogenic effect of pyrethroids.
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http://dx.doi.org/10.1002/lipd.12234DOI Listing
May 2020

Polystyrene microplastic exposure disturbs hepatic glycolipid metabolism at the physiological, biochemical, and transcriptomic levels in adult zebrafish.

Sci Total Environ 2020 Mar 27;710:136279. Epub 2019 Dec 27.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Microplastics (MPs), which are new types of environmental pollutants, have recently received widespread attention worldwide. MPs can accumulate in the bodies of animals and in plants, and they can also enter the human body through the food chain. However, knowledge of the effects of MPs on the health of animals is still limited. In this experiment, adult male zebrafish were exposed to 20 or 100 μg/L of 5 μm polystyrene MP for 21 days in an attempt to determine the hepatic effects related to glycolipid metabolism at the biochemical and transcriptomic levels. It was found that body weight and condition factor decreased significantly in zebrafish after exposure to 20 and 100 μg/L polystyrene MP for 21 days. The transcription levels of major genes related to glycolipid metabolism decreased significantly in the liver. Correspondingly, the levels of major biochemical parameters, including Glu, pyruvic acid, α-ketoglutaric acid and IDH, were also decreased in the livers of exposed zebrafish, especially those in the 100 μg/L polystyrene MP-treated group. Moreover, the data on the hepatic transcriptome also confirmed that some genes related to fatty acid metabolism, amino acid metabolism and carbon metabolism tended to be decreased in the livers of exposed zebrafish. Taken together, our data confirmed that polystyrene PS-MP can induce hepatic glycolipid metabolism disorder at the physiological, biochemical, and transcriptomic levels in adult zebrafish after 21 days of exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136279DOI Listing
March 2020

The emerging PFOS alternative OBS exposure induced gut microbiota dysbiosis and hepatic metabolism disorder in adult zebrafish.

Comp Biochem Physiol C Toxicol Pharmacol 2020 Apr 7;230:108703. Epub 2020 Jan 7.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Sodium ρ-perfluorous nonenoxybenzene sulfonate (OBS), as a novel the alternatives of PFASs, is widely used in many fields of life. Here, adult male zebrafish selected were exposed to OBS at concentrations of 3, 30 and 300 μg/L for 7 and 21 days, respectively. Based on the gut microbiota analysis, at genus level, the relative abundance of the Flavobacterium, Hyphomicrobium, Paracoccus, Lawsonia, Plesiomonas and Vibrio changed significantly in the gut of zebrafish after exposure to 300 μg/L OBS. In addition, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis suggested that a total of 1077 metabolites in pos-model and a total of 706 metabolites in neg-model changed significantly from the liver, and these changed metabolites were tightly related to several pathways including amino acid, pyrimidine and purine metabolism, etc. Furthermore, the changed gut bacteria including Flavobacterium, Hyphomicrobium, Paracoccus, Lawsonia, Plesiomonas and Vibrio at genus level were significantly correlated with various metabolites (succinic acid, leucine, xanthine, orotic acid, nicotinic acid, etc.). Taken together, all the results showed that low dose of OBS exposure could induce the dysbiosis of gut microbiota and disturbed the hepatic metabolism balance in adult male zebrafish.
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http://dx.doi.org/10.1016/j.cbpc.2020.108703DOI Listing
April 2020

Imidacloprid disrupts the endocrine system by interacting with androgen receptor in male mice.

Sci Total Environ 2020 Mar 20;708:135163. Epub 2019 Nov 20.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

In the current study, six-week-old male ICR mice were administered imidacloprid (IMI) at concentrations of 3, 10 and 30 mg/L for a duration of 10 weeks to investigate the toxicity of IMI on the endocrine system. We observed that testicular morphology was severely impaired and damaged, and the levels of serum testosterone (T) and the expression of androgen receptor (AR) decreased significantly. Molecular docking analysis suggested that IMI docks into the active site of AR successfully and that three key hydrogen bonds were formed with the active site residues Glu11, Gln41 and Lys138. The binding free energy value of the AR-IMI complex suggested a stable binding between IMI and AR. All these results indicated that IMI could interact with AR. In addition, major genes in the testis involved in the synthesis of cholesterol and T were generally inhibited, and the serum cholesterol sources were also reduced. Moreover, the aromatase in male mice was lacking after subchronic IMI exposure. The data acquired from the present study indicated that IMI could lead to endocrine disruption by interacting with AR and influence the expression of genes involved in the production of T in male mice.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135163DOI Listing
March 2020

Tetrabromoethylcyclohexane (TBECH) exhibits immunotoxicity in murine macrophages.

Environ Toxicol 2020 Feb 7;35(2):159-166. Epub 2019 Nov 7.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.

Tetrabromoethylcyclohexane (TBECH) has been linked to endocrine disruption, hepatotoxicity, and reproductive toxicity. However, its immunotoxicity remains largely unknown. In the present study, RAW 264.7 cells, mouse macrophage cell line, were exposed to TBECH. MTT assays showed that TBECH significantly enhanced lactate dehydrogenase (LDH) release in RAW 264.7 cells. The mRNA expression of some proapoptotic genes was upregulated by TBECH. Accordingly, TBECH elevated caspase-3 activity. In addition, TBECH upregualted the mRNA levels of some pro-inflammatory cytokines, whereas it downregulated LPS-stimulated mRNA expression of these cytokines. Moreover, TBECH downregulated the mRNA expression of selected antigen presenting-related genes. Furthermore, TBECH increased reactive oxygen species level, reduced glutathione content and the activities of superoxide dismutase and catalase, and upregulated the mRNA expression of selected oxidative stress-related genes. The obtained data demonstrated that TBECH exhibits immunotoxicity in macrophages, and will help to evaluate its health risks.
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http://dx.doi.org/10.1002/tox.22852DOI Listing
February 2020

The regulation of autophagy in the pesticide-induced toxicity: Angel or demon?

Chemosphere 2020 Mar 17;242:125138. Epub 2019 Oct 17.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Pesticides have become an essential tool for pest kill, weed control and microbiome inhibition for both agricultural and domestic use. However, with the massive use, pesticides can exist in soil, air and water, and sometimes even accumulate in the human or other mammals through food chains. Lots of researches have proven that pesticides possess toxicity to mammals on endocrine, neural and immune systems. Autophagy, as a conservative intracellular process, which is activated by stress-related signals, plays a pivotal role, either "angle" or "demon", in regulation of cell fate and function. Recent evidences in researches elucidated a strong link between the autophagy and the toxicity of pesticides. In this review, we summarized the previous researches which focus on the autophagy regulation in the pesticides-induced toxicity, and hope that this work can help us to discover a potential strategy for the treatment of the disease caused by pesticides.
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http://dx.doi.org/10.1016/j.chemosphere.2019.125138DOI Listing
March 2020

Bioconcentration and Metabolic Effects of Emerging PFOS Alternatives in Developing Zebrafish.

Environ Sci Technol 2019 Nov 25;53(22):13427-13439. Epub 2019 Oct 25.

Department of Biology , University of Ottawa , Ottawa , Ontario K1N 6N5 , Canada.

The novel PFOS alternatives, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) and sodium -perfluorous nonenoxybenzenesulfonate (OBS), are emerging in the Chinese market, but little is known about their ecological risks. In this study, zebrafish embryos were exposed to PFOS, F-53B, and OBS to evaluate their bioconcentration and acute metabolic consequences. Per- and polyfluoroalkyl substances (PFASs) accumulated in larvae in the order of F-53B > PFOS > OBS, with the bioconcentration factors ranging from 20 to 357. Exposure to F-53B and PFOS, but not OBS, increased energy expenditure, and reduced feed intake in a concentration-dependent manner and the expression of genes involved in metabolic pathways at the transcriptional and translational levels. Molecular docking revealed that the binding affinities of PFASs to glucokinase were decreased in the following order: F-53B > PFOS > OBS. Finally, the results of Point of Departure (PoD) indicate that metabolic end points at the molecular and organismal level are most sensitive to F-53B followed by PFOS and OBS. Collectively, F-53B has the highest bioconcentration potential and the strongest metabolism-disrupting effects, followed by PFOS and OBS. Our findings have important implications for the assessment of early developmental metabolic effects of PFOS alternatives F-53B and OBS in wildlife and humans.
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http://dx.doi.org/10.1021/acs.est.9b03820DOI Listing
November 2019

Maternal exposure to different sizes of polystyrene microplastics during gestation causes metabolic disorders in their offspring.

Environ Pollut 2019 Dec 30;255(Pt 1):113122. Epub 2019 Aug 30.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Microplastics (MPs) are highly concerned environmental pollutants that are ubiquitous in the environmental and might affect human and animal health. In this study, we exposed pregnant mice to 0.5 and 5 μm with 100 and 1000 μg/L polystyrene MPs, then investigated maternal MPs exposure during gestation and evaluated the potential effects on the mice offspring (PND42). In the F1 offspring, the serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels and hepatic TC, TG levels were altered, while some of them were only significant in 5 μm MPs-treated group. Various serum metabolites including amino acids and acyl-carnitines were carried out by nonderivatized tandem mass spectrometry, there were 11 and 15 kinds of metabolites changes significantly in 0.5 and 5 μm MPs-treated groups, respectively. Furthermore, the changes of C0 and C0/(C16 + 18) indicators suggested the potential risk of fatty acid metabolism disorder, which was verified by hepatic genes expression. These results indicated that maternal exposure of two different sizes of polystyrene MPs increased risks of metabolic disorder in their offspring, and greater effects were observed in 5 μm MPs-treated groups. The data provides a preliminary exploration of the potential relationship between MPs and the risk metabolic disorder even in the next generation, which might offer new insights into the health risk assessment of MPs.
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http://dx.doi.org/10.1016/j.envpol.2019.113122DOI Listing
December 2019

Maternal Polystyrene Microplastic Exposure during Gestation and Lactation Altered Metabolic Homeostasis in the Dams and Their F1 and F2 Offspring.

Environ Sci Technol 2019 Sep 4;53(18):10978-10992. Epub 2019 Sep 4.

College of Biotechnology and Bioengineering , Zhejiang University of Technology , Hangzhou 310032 , China.

Microplastics (MPs) are considered as a pollutant of marine environments and have become a global environmental problem in recent years. A number of studies have demonstrated that MPs can enter the human food chain, and MPs have even been detected in human stools. Therefore, there is increasing concern about the potential risks of MPs to human and animal health. Here, we investigated maternal polystyrene MPs exposure during gestation and lactation and evaluated the potential effects on dams and the F1 (both PND 42 and 280) and F2 (PND 42) generations. The results of transcriptome and 16S rRNA sequencing indicated that MPs caused the metabolic disorder in maternal MPs associated with gut microbiota dysbiosis and gut barrier dysfunction. Simultaneously, maternal MPs exposure also had the intergenerational effects and even caused long-term metabolic consequences in the F1 and F2 generations. In addition, in F1 (PND 42), the composition of gut microbiota did not change significantly, while the hepatic transcriptome and serum metabolite changes showed the potential risk in metabolic disorder. Then, the potential of hepatic lipid accumulation was observed in adult F1 mice (PND 280), especially in the female mice. Our results demonstrated that maternal MPs exposure during gestation and lactation increases the risk of metabolic disorder, and these results provide new insight into the potential long-term hazards of MPs.
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http://dx.doi.org/10.1021/acs.est.9b03191DOI Listing
September 2019