As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many fields.Currently,information on the cardiotoxicity induced by BP-QDs remains limited.We aimed to eval...As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many fields.Currently,information on the cardiotoxicity induced by BP-QDs remains limited.We aimed to evaluate BP-QD-induced cardiac toxicity in mice.Histopathological examination of heart tissue sections was performed.Transcriptome sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related genes.We found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 days.In addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated groups.Altered expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory responses.In addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling pathways.The expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling pathway.Our study provides new insights into the toxicity of BP-QDs to human health.展开更多
Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life ...Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid(FA).Specifically,after early-life exposure(1–21 days postfertilization,dpf)to TBT(0,1,10 and 100 ng/L),zebrafish(Danio rerio)were cultured in clean medium until sexual maturity.The exposed females were mated with unexposed males to produce embryos(F1).The F1 generation were cultured(4–120 hours post-fertilization,hpf)with and without 1 mmol/L FA.The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring(F1)were significantly enhanced anxiety and reduced aggression,decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body.Moreover,the intergenerational neurodevelopmental toxicity,as manifested in the F1 generation,was attenuated by FA supplementation.In summary,early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish,and DNA methyl donors had a protective effect on F1 neurodevelopment,which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.展开更多
Neburon is a phenylurea herbicide that is widely used worldwide,but its toxicity is poorly studied.In our previous study,we found that neburon has strong aryl hydrocarbon receptor(AhR)agonist activity,but whether it c...Neburon is a phenylurea herbicide that is widely used worldwide,but its toxicity is poorly studied.In our previous study,we found that neburon has strong aryl hydrocarbon receptor(AhR)agonist activity,but whether it causes reproductive toxicity is not clear.In the present study,zebrafish were conducted as a model organism to evaluate whether environmental concentrations of neburon(0.1,1 and 10μg/L)induce reproductive disorder in males.After exposure to neburon for 150 days from embryo to adult,that the average spawning egg number in high concentration group was 106.40,which was significantly lower than 193.00in control group.This result was mainly due to the abnormal male reproductive behavior caused by abnormal transcription of genes associated with reproductive behavior in the brain,such as secretogranin-2a.The proportions of spermatozoa in the medium and high concentration groups were 82.40%and 83.84%,respectively,which were significantly lower than 89.45%in control group.This result was mainly caused by hormonal disturbances and an increased proportion of apoptotic cells.The hormonal disruption was due to the significant changes in the transcription levels of key genes in the hypothalamus-pituitary-gonadal axis following neburon treatment.Neburon treatment also significantly activated the AhR signaling pathway,causing oxidative stress damage and eventually leading to a significant increase in apoptosis in the exposed group.Together,these data filled the currently more vacant profile of neburon toxicity and might provide information to assess the ecotoxicity of neburon on male reproduction at environmentally relevant concentrations.展开更多
The wide use of pesticides has seriously threatened human health and the survival of beneficial organisms. The fungicide mepanipyrim is widely used in viticulture practices. Studies of mepanipyrim-induced toxicity in ...The wide use of pesticides has seriously threatened human health and the survival of beneficial organisms. The fungicide mepanipyrim is widely used in viticulture practices. Studies of mepanipyrim-induced toxicity in organisms are still scarce, especially studies on cardiotoxicity. In this study, we aimed to investigate mepanipyrim-induced cardiotoxicity in zebrafish(Danio rerio) larvae. We found that mepanipyrim could induce cardiotoxicity by altering the heart rate and cardiomyocyte diameter of larvae. Meanwhile, RNA sequencing and RT-qPCR data indicated that mepanipyrim exposure could dramatically alter the m RNA expression of calcium signaling pathway-, cardiac muscle contraction-, and oxidative respiratory chain-related genes. Interestingly, by the CALUX cell bioassay, we found that most cytochrome c oxidase(COX) family genes exhibited potential AhR-regulated activity, suggesting that mepanipyrim induced cardiotoxicity via a novel AhR-regulated manner in larvae.Additionally, the AhR antagonist CH_(2)23191 could effectively prevent mepanipyrim-induced cardiotoxicity in zebrafish larvae. In conclusion, the AhR agonist mepanipyrim could induce cardiotoxicity in a novel unreported AhR-regulated manner, which could specifically affect the expression of COX family genes involved in the mitochondrial oxidative respiratory chain. Our data will help explain the toxic effects of mepanipyrim on organisms and provide new insight into the AhR agonistic activity pesticide-induced cardiotoxicity.展开更多
Mepanipyrim,an anilinopyrimidine fungicide,has been extensively used to prevent fungal diseases in fruit culture.Currently,research on mepanipyrim-induced toxicity in organisms is still very scarce,especially visual d...Mepanipyrim,an anilinopyrimidine fungicide,has been extensively used to prevent fungal diseases in fruit culture.Currently,research on mepanipyrim-induced toxicity in organisms is still very scarce,especially visual developmental toxicity.Here,zebrafish larvae were employed to investigate mepanipyrim-induced visual developmental toxicity.Intense light andmonochromatic light stimuli-evoked escape experiments were used to investigate vision-guided behaviors.Meanwhile,transcriptomic sequencing and real-time quantitative PCR assays were applied to assess the potential mechanisms of mepanipyrim-induced visual developmental toxicity and vision-guided behavioral alteration.Our results showed that mepanipyrim exposure could induce retinal impairment and vision-guided behavioral alteration in larval zebrafish.In addition,the grk1b gene of the phototransduction signaling pathway was found to be a potential aryl hydrocarbon receptor(AhR)-regulated gene.Mepanipyrim-induced visual developmental toxicity was potentially related to the AhR signaling pathway.Furthermore,mepanipyrim-induced behavioral alteration was guided by the visual function,and the effects of mepanipyrim on long and middle wavelength light-sensitive opsins may be the main cause of vision-guided behavioral alteration.Our results provide insights into understanding the relationship between visual development and vision-guided behaviors induced by mepanipyrim exposure.展开更多
This study was conducted to assess the effects of difenoconazole（DFZ）, a triazole fungicide,on the hepatic biotransformation system and its bioaccumulation in marine medaka（Oryzias melastigma）. Fish were exposed t...This study was conducted to assess the effects of difenoconazole（DFZ）, a triazole fungicide,on the hepatic biotransformation system and its bioaccumulation in marine medaka（Oryzias melastigma）. Fish were exposed to DFZ（1, 10, 100, 1000 ng/L） for 180 days. The results showed that：（1） The m RNA levels of hepatic CYP1A1, CYP1 B, CYP1C1, CYP27 B and CYP3A40 were up-regulated, but those of CYP3A38 and CYP27A1 were down-regulated.（2） The activity of ethoxyresorufin-O-deethylase（EROD） and the content of reduced glutathione（GSH） in the liver were increased in the DFZ-treated groups, and glutathione S-transferase（GST） activity was increased in the 100 and 1000 ng/L groups.（3） DFZ was accumulated in the muscle and the biological concentration factors in the 10, 100, and1000 ng/L groups were respectively 149, 81 and 25. These results suggested that long-term exposure to DFZ at low concentrations would result in a bioaccumulation of this compound and disturb the biotransformation system.展开更多
Quantum dots(QDs)are new types of nanomaterials.Few studies have focused on the effect of different surface modified QDs on embryonic development.Herein,we compared the in vivo toxicity of Cd Se/Zn S QDs with carboxyl...Quantum dots(QDs)are new types of nanomaterials.Few studies have focused on the effect of different surface modified QDs on embryonic development.Herein,we compared the in vivo toxicity of Cd Se/Zn S QDs with carboxyl(-COOH)and amino(-NH 2)modification using zebrafish embryos.After exposure,the two Cd Se/Zn S QDs decreased the survival rate,hatching rate,and embryo movement of zebrafish.Moreover,we found QDs attached to the embryo membrane before hatching and the eyes,yolk and heart after hatching.The attached amount of carboxyl QDs was more.Consistently,the Cd content in embryos and larvae was higher in carboxyl QD-treatment.We further observed that the two QDs caused zebrafish pericardial edema and cardiac dysfunction.In line with it,both carboxyl and amino QDs upregulated the transcription levels of cardiac development-related genes,and the levels were higher in carboxyl QD-treated groups.Furthermore,the chelator of Cd^2+diethylene triamine pentacetate acid could partially rescued the developmental toxicity caused by the two types of QDs suggesting that both the nature of QDs and the release of Cd^2+contribute to the developmental toxicity.In conclusion,the two Cd Se/ZnS QDs have developmental toxicity and affect the cardiac development,and the carboxyl QDs is more toxic possibly due to the higher affinity and more release to embryos and larvae.Our study provides new knowledge that the surface functional modification of QDs is critical on the development on aquatic species,which is beneficial to develop and applicate QDs more safely and environmentfriendly.展开更多
Difenoconazole（DFZ） is a triazole fungicide which has been detected in the aquatic environment, including estuaries and embayments. However, few studies addressing the reproductive toxicity and transgenerational eff...Difenoconazole（DFZ） is a triazole fungicide which has been detected in the aquatic environment, including estuaries and embayments. However, few studies addressing the reproductive toxicity and transgenerational effects of DFZ on marine fishes are available.The present study was conducted to investigate the effects of DFZ on male marine medaka（Oryzias melastigma）. After exposure of the embryo to 1, 10, 100 and 1000 ng/L DFZ for180 days, the gonadosomatic index was significantly decreased in the 1000 ng/L treatment.The number of sperm was reduced while the abundances of spermatocytes and spermatogonia in the testes were increased in all the treatments. The m RNA levels of salmontype gnrh（sgnrh）, the luteinizing hormone（lhβ） and the follicle-stimulating hormone（fshβ）genes in the brain all exhibited a significant down-regulation, the expression of androgen receptors（arα and arβ） was decreased and that of estrogen receptor β and cytochrome P450 aromatase（cyp19 B） was increased in the testes. The expression levels of cyp19 A and cyp19 B were increased in the liver. The decrease of ars m RNA levels might be one of the reasons causing the reduction of sperm. The down-regulation of sgnrh, lhβ and fshβ m RNA levels suggested that DFZ might impact the spermatogenesis via the brain–pituitary–gonad pathway. The decrease of the fertilization success, the hatch ability and the swim-up success in the F1 generation indicated that DFZ pollution at environmental levels might cause a decrease of wild fish populations.展开更多
Metalaxyl is an anilide pesticide that is widely used to control plant diseases caused by Peronosporales species.In order to study the toxic effects,zebrafish embryos were exposed to metalaxyl at nominal concentration...Metalaxyl is an anilide pesticide that is widely used to control plant diseases caused by Peronosporales species.In order to study the toxic effects,zebrafish embryos were exposed to metalaxyl at nominal concentrations of 5,50 and 500 ng/L for 72 hr,and the cardiac development and functioning of larvae were observed.The results showed that metalaxyl exposure resulted in increased rates of pericardial edema,heart hemorrhage and cardiac malformation.The distance between the sinus venosus and bulbus arteriosus,stroke volume,cardiac output and heart rate were significantly increased in larvae exposed to 50 and 500 ng/L metalaxyl compared to solvent control larvae.Significant upregulation in the transcription of tbx5,gata4 and myh6 was observed in the 50 and 500 ng/L treatments,and that of nkx2.5 and myl7 was observed in the 5,50 and 500 ng/L groups.These disturbances may be related to cardiac developmental and functional defects in the larvae.The activity of Na+/K+-ATPase and Ca2+-ATPase was significantly increased in zebrafish embryos exposed to 500 ng/L metalaxyl,and the mRNA levels of genes related to ATPase (atp2a11,atp1b2b,and atp1a3b)(in the 50 and 500 ng/L groups) and calcium channels (cacna1ab)(in the 500 ng/L group) were significantly downregulated;these changes might be associated with heart arrhythmia and functional failure.展开更多
The toxic effects of tributyltin（TBT） have been extensively documented in several types of cells, but the molecular mechanisms related to the genotoxic effects of TBT have still not been fully elucidated. Our study ...The toxic effects of tributyltin（TBT） have been extensively documented in several types of cells, but the molecular mechanisms related to the genotoxic effects of TBT have still not been fully elucidated. Our study showed that exposure of human hepatoma G2 cells to 1–4 μmol/L TBT for 3 hr caused severe DNA damage in a concentration-dependent manner. Moreover, the expression levels of key DNA damage sensor genes such as the replication factor C, proliferating cell nuclear antigen and poly（ADP-ribose）polymerase-1 were inhabited in a concentration-dependent manner. We further demonstrated that TBT induced cell apoptosis via the p53-mediated pathway, which was most likely activated by the ataxia telangiectasia mutated and rad-3 related（ATR）protein kinase. The results also showed that cytochrome c, caspase-3, caspase-8,caspase-9, and the B-cell lymphoma 2 were involved in this process. Taken together, we demonstrated for the first time that the inhibition of the DNA repair system might be more responsible for TBT-induced genotoxic effects in cells. Then the generated DNA damage induced by TBT initiated ATR-p53-mediated apoptosis.展开更多
基金supported by the National Natural Science Foundation of China (Nos.32071301 and 31971234)。
文摘As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many fields.Currently,information on the cardiotoxicity induced by BP-QDs remains limited.We aimed to evaluate BP-QD-induced cardiac toxicity in mice.Histopathological examination of heart tissue sections was performed.Transcriptome sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related genes.We found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 days.In addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated groups.Altered expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory responses.In addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling pathways.The expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling pathway.Our study provides new insights into the toxicity of BP-QDs to human health.
基金supported by the National Natural Science Foundation of China (Nos.32071301,31971234 and 42177411)the Natural Science Foundation of Fujian Province,China (No.2020J01027)。
文摘Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid(FA).Specifically,after early-life exposure(1–21 days postfertilization,dpf)to TBT(0,1,10 and 100 ng/L),zebrafish(Danio rerio)were cultured in clean medium until sexual maturity.The exposed females were mated with unexposed males to produce embryos(F1).The F1 generation were cultured(4–120 hours post-fertilization,hpf)with and without 1 mmol/L FA.The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring(F1)were significantly enhanced anxiety and reduced aggression,decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body.Moreover,the intergenerational neurodevelopmental toxicity,as manifested in the F1 generation,was attenuated by FA supplementation.In summary,early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish,and DNA methyl donors had a protective effect on F1 neurodevelopment,which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.
基金supported by the National Natural Science Foundation of China(No.42177411)。
文摘Neburon is a phenylurea herbicide that is widely used worldwide,but its toxicity is poorly studied.In our previous study,we found that neburon has strong aryl hydrocarbon receptor(AhR)agonist activity,but whether it causes reproductive toxicity is not clear.In the present study,zebrafish were conducted as a model organism to evaluate whether environmental concentrations of neburon(0.1,1 and 10μg/L)induce reproductive disorder in males.After exposure to neburon for 150 days from embryo to adult,that the average spawning egg number in high concentration group was 106.40,which was significantly lower than 193.00in control group.This result was mainly due to the abnormal male reproductive behavior caused by abnormal transcription of genes associated with reproductive behavior in the brain,such as secretogranin-2a.The proportions of spermatozoa in the medium and high concentration groups were 82.40%and 83.84%,respectively,which were significantly lower than 89.45%in control group.This result was mainly caused by hormonal disturbances and an increased proportion of apoptotic cells.The hormonal disruption was due to the significant changes in the transcription levels of key genes in the hypothalamus-pituitary-gonadal axis following neburon treatment.Neburon treatment also significantly activated the AhR signaling pathway,causing oxidative stress damage and eventually leading to a significant increase in apoptosis in the exposed group.Together,these data filled the currently more vacant profile of neburon toxicity and might provide information to assess the ecotoxicity of neburon on male reproduction at environmentally relevant concentrations.
基金supported by the National Natural Science Foundation of China (Nos. 42177411 and 31971234)。
文摘The wide use of pesticides has seriously threatened human health and the survival of beneficial organisms. The fungicide mepanipyrim is widely used in viticulture practices. Studies of mepanipyrim-induced toxicity in organisms are still scarce, especially studies on cardiotoxicity. In this study, we aimed to investigate mepanipyrim-induced cardiotoxicity in zebrafish(Danio rerio) larvae. We found that mepanipyrim could induce cardiotoxicity by altering the heart rate and cardiomyocyte diameter of larvae. Meanwhile, RNA sequencing and RT-qPCR data indicated that mepanipyrim exposure could dramatically alter the m RNA expression of calcium signaling pathway-, cardiac muscle contraction-, and oxidative respiratory chain-related genes. Interestingly, by the CALUX cell bioassay, we found that most cytochrome c oxidase(COX) family genes exhibited potential AhR-regulated activity, suggesting that mepanipyrim induced cardiotoxicity via a novel AhR-regulated manner in larvae.Additionally, the AhR antagonist CH_(2)23191 could effectively prevent mepanipyrim-induced cardiotoxicity in zebrafish larvae. In conclusion, the AhR agonist mepanipyrim could induce cardiotoxicity in a novel unreported AhR-regulated manner, which could specifically affect the expression of COX family genes involved in the mitochondrial oxidative respiratory chain. Our data will help explain the toxic effects of mepanipyrim on organisms and provide new insight into the AhR agonistic activity pesticide-induced cardiotoxicity.
基金supported by the National Natural Science Foundation of China (No.42177411)the Natural Science Foundation of Fujian Province of China (No.2018J01067)
文摘Mepanipyrim,an anilinopyrimidine fungicide,has been extensively used to prevent fungal diseases in fruit culture.Currently,research on mepanipyrim-induced toxicity in organisms is still very scarce,especially visual developmental toxicity.Here,zebrafish larvae were employed to investigate mepanipyrim-induced visual developmental toxicity.Intense light andmonochromatic light stimuli-evoked escape experiments were used to investigate vision-guided behaviors.Meanwhile,transcriptomic sequencing and real-time quantitative PCR assays were applied to assess the potential mechanisms of mepanipyrim-induced visual developmental toxicity and vision-guided behavioral alteration.Our results showed that mepanipyrim exposure could induce retinal impairment and vision-guided behavioral alteration in larval zebrafish.In addition,the grk1b gene of the phototransduction signaling pathway was found to be a potential aryl hydrocarbon receptor(AhR)-regulated gene.Mepanipyrim-induced visual developmental toxicity was potentially related to the AhR signaling pathway.Furthermore,mepanipyrim-induced behavioral alteration was guided by the visual function,and the effects of mepanipyrim on long and middle wavelength light-sensitive opsins may be the main cause of vision-guided behavioral alteration.Our results provide insights into understanding the relationship between visual development and vision-guided behaviors induced by mepanipyrim exposure.
基金supported by the National Natural Science Foundation of China(No.41376118)
文摘This study was conducted to assess the effects of difenoconazole（DFZ）, a triazole fungicide,on the hepatic biotransformation system and its bioaccumulation in marine medaka（Oryzias melastigma）. Fish were exposed to DFZ（1, 10, 100, 1000 ng/L） for 180 days. The results showed that：（1） The m RNA levels of hepatic CYP1A1, CYP1 B, CYP1C1, CYP27 B and CYP3A40 were up-regulated, but those of CYP3A38 and CYP27A1 were down-regulated.（2） The activity of ethoxyresorufin-O-deethylase（EROD） and the content of reduced glutathione（GSH） in the liver were increased in the DFZ-treated groups, and glutathione S-transferase（GST） activity was increased in the 100 and 1000 ng/L groups.（3） DFZ was accumulated in the muscle and the biological concentration factors in the 10, 100, and1000 ng/L groups were respectively 149, 81 and 25. These results suggested that long-term exposure to DFZ at low concentrations would result in a bioaccumulation of this compound and disturb the biotransformation system.
基金the National Natural Science Foundation of China(No.31971234)the Fundamental Research Funds for the Central Universities(No.20720180045)the Open Research Fund of State Key Laboratory of Cellular Stress Biology,Xiamen University(No.SKLCSB2019KF001)。
文摘Quantum dots(QDs)are new types of nanomaterials.Few studies have focused on the effect of different surface modified QDs on embryonic development.Herein,we compared the in vivo toxicity of Cd Se/Zn S QDs with carboxyl(-COOH)and amino(-NH 2)modification using zebrafish embryos.After exposure,the two Cd Se/Zn S QDs decreased the survival rate,hatching rate,and embryo movement of zebrafish.Moreover,we found QDs attached to the embryo membrane before hatching and the eyes,yolk and heart after hatching.The attached amount of carboxyl QDs was more.Consistently,the Cd content in embryos and larvae was higher in carboxyl QD-treatment.We further observed that the two QDs caused zebrafish pericardial edema and cardiac dysfunction.In line with it,both carboxyl and amino QDs upregulated the transcription levels of cardiac development-related genes,and the levels were higher in carboxyl QD-treated groups.Furthermore,the chelator of Cd^2+diethylene triamine pentacetate acid could partially rescued the developmental toxicity caused by the two types of QDs suggesting that both the nature of QDs and the release of Cd^2+contribute to the developmental toxicity.In conclusion,the two Cd Se/ZnS QDs have developmental toxicity and affect the cardiac development,and the carboxyl QDs is more toxic possibly due to the higher affinity and more release to embryos and larvae.Our study provides new knowledge that the surface functional modification of QDs is critical on the development on aquatic species,which is beneficial to develop and applicate QDs more safely and environmentfriendly.
基金supported by the National Natural Science Foundation of China (No. 41376118)
文摘Difenoconazole（DFZ） is a triazole fungicide which has been detected in the aquatic environment, including estuaries and embayments. However, few studies addressing the reproductive toxicity and transgenerational effects of DFZ on marine fishes are available.The present study was conducted to investigate the effects of DFZ on male marine medaka（Oryzias melastigma）. After exposure of the embryo to 1, 10, 100 and 1000 ng/L DFZ for180 days, the gonadosomatic index was significantly decreased in the 1000 ng/L treatment.The number of sperm was reduced while the abundances of spermatocytes and spermatogonia in the testes were increased in all the treatments. The m RNA levels of salmontype gnrh（sgnrh）, the luteinizing hormone（lhβ） and the follicle-stimulating hormone（fshβ）genes in the brain all exhibited a significant down-regulation, the expression of androgen receptors（arα and arβ） was decreased and that of estrogen receptor β and cytochrome P450 aromatase（cyp19 B） was increased in the testes. The expression levels of cyp19 A and cyp19 B were increased in the liver. The decrease of ars m RNA levels might be one of the reasons causing the reduction of sperm. The down-regulation of sgnrh, lhβ and fshβ m RNA levels suggested that DFZ might impact the spermatogenesis via the brain–pituitary–gonad pathway. The decrease of the fertilization success, the hatch ability and the swim-up success in the F1 generation indicated that DFZ pollution at environmental levels might cause a decrease of wild fish populations.
基金supported by the National Natural Science Foundation of China(No.41376118)
文摘Metalaxyl is an anilide pesticide that is widely used to control plant diseases caused by Peronosporales species.In order to study the toxic effects,zebrafish embryos were exposed to metalaxyl at nominal concentrations of 5,50 and 500 ng/L for 72 hr,and the cardiac development and functioning of larvae were observed.The results showed that metalaxyl exposure resulted in increased rates of pericardial edema,heart hemorrhage and cardiac malformation.The distance between the sinus venosus and bulbus arteriosus,stroke volume,cardiac output and heart rate were significantly increased in larvae exposed to 50 and 500 ng/L metalaxyl compared to solvent control larvae.Significant upregulation in the transcription of tbx5,gata4 and myh6 was observed in the 50 and 500 ng/L treatments,and that of nkx2.5 and myl7 was observed in the 5,50 and 500 ng/L groups.These disturbances may be related to cardiac developmental and functional defects in the larvae.The activity of Na+/K+-ATPase and Ca2+-ATPase was significantly increased in zebrafish embryos exposed to 500 ng/L metalaxyl,and the mRNA levels of genes related to ATPase (atp2a11,atp1b2b,and atp1a3b)(in the 50 and 500 ng/L groups) and calcium channels (cacna1ab)(in the 500 ng/L group) were significantly downregulated;these changes might be associated with heart arrhythmia and functional failure.
基金supported by the National Natural Science Foundation of China (No. 40606027)the Project of the Xiamen Science and Technology Program (No. 2013Z20134027)
文摘The toxic effects of tributyltin（TBT） have been extensively documented in several types of cells, but the molecular mechanisms related to the genotoxic effects of TBT have still not been fully elucidated. Our study showed that exposure of human hepatoma G2 cells to 1–4 μmol/L TBT for 3 hr caused severe DNA damage in a concentration-dependent manner. Moreover, the expression levels of key DNA damage sensor genes such as the replication factor C, proliferating cell nuclear antigen and poly（ADP-ribose）polymerase-1 were inhabited in a concentration-dependent manner. We further demonstrated that TBT induced cell apoptosis via the p53-mediated pathway, which was most likely activated by the ataxia telangiectasia mutated and rad-3 related（ATR）protein kinase. The results also showed that cytochrome c, caspase-3, caspase-8,caspase-9, and the B-cell lymphoma 2 were involved in this process. Taken together, we demonstrated for the first time that the inhibition of the DNA repair system might be more responsible for TBT-induced genotoxic effects in cells. Then the generated DNA damage induced by TBT initiated ATR-p53-mediated apoptosis.
