Perfluorobutanesulfonate(PFBS)is an emerging pollutant capable of potently disrupting the sex and thyroid endocrine systems of teleosts.However,the hypoxic and temporal variation in PFBS endocrine disrupting toxicity ...Perfluorobutanesulfonate(PFBS)is an emerging pollutant capable of potently disrupting the sex and thyroid endocrine systems of teleosts.However,the hypoxic and temporal variation in PFBS endocrine disrupting toxicity remain largely unknown.In the present study,adult marine medaka were exposed to environmentally realistic concentrations of PFBS(0 and 10μg/L)under normoxia or hypoxia conditions for 7 days,aiming to explore the interactive behavior between PFBS and hypoxia.In addition,PFBS singular exposure was extended till 21days under normoxia to elucidate the time-course progression in PFBS toxicity.The results showed that hypoxia inhibited the growth and caused the suspension of egg spawn regardless of PFBS exposure.With regard to the sex endocrine system,7-day PFBS exposure led to an acute stimulation of transcriptional profiles in females,which,subsequently,recovered after the 21-day exposure.The potency of hypoxia to disturb the sex hormones was much stronger than PFBS.A remarkable increase in estradiol concentration was noted in medaka blood after hypoxia exposure.Changes in sex endocrinology of coexposed fish were largely determined by hypoxia,which drove the formation of an estrogenic environment.PFBS further enhanced the endocrine disrupting effects of hypoxia.However,the hepatic synthesis of vitellogenin and choriogenin,two commonly used sensitive biomarkers of estrogenic activity,failed to initiate in response to the estrogen stimulus.Compared to sex endocrine system,disturbances in thyroidal axis by PFBS or hypoxia were relatively mild.Overall,the present findings will advance our toxicological understanding about PFBS pollutant under the interference of hypoxia.展开更多
To protect the wellbeing of research animals,certain non-invasive measures are in increasing need to facilitate an early diagnosis of health and toxicity.In this study,feces specimen was collected from adult zebrafish...To protect the wellbeing of research animals,certain non-invasive measures are in increasing need to facilitate an early diagnosis of health and toxicity.In this study,feces specimen was collected from adult zebrafish to profile the metabolome fingerprint.Variability in fecal metabolite composition was also distinguished as a result of aging,perfluorobutanesulfonate(PFBS)toxicant,and fecal transplantation.The results showed that zebrafish feces was very rich in a diversity of metabolites that belonged to several major classes,including lipid,amino acid,carbohydrate,vitamin,steroid hormone,and neurotransmitter.Fecal metabolites had functional implications to multiple physiological activities,which were characterized by the enrichment of digestion,absorption,endocrine,and neurotransmission processes.The high richness and functional involvement of fecal metabolites pinpointed feces as an abundant source of diagnostic markers.By comparison between young and aged zebrafish,fundamental modifications of fecal metabolomes were caused by aging progression,centering on the neuroactive ligand-receptor interaction pathway.Exposure of aged zebrafish to PFBS pollutant also significantly disrupted the metabolomic structure in feces.Of special concern were the changes in fecal hormone intermediates after PFBS exposure,which was concordant with the in vivo endocrine disrupting effects of PFBS.Furthermore,itwas intriguing that transplantation of young zebrafish feces efficientlymitigated the metabolic perturbation of PFBS in aged recipients,highlighting the health benefits of therapeutic strategies based on gut microbiota manipulation.In summary,the present study provides preliminary clues to evidence the non-invasive advantage of fecal metabolomics in the early diagnosis and prediction of physiology and toxicology.展开更多
Methylparaben(MeP)is an emerging aquatic pollutant that is found to impact neural functions.However,it still lacks a comprehensive understanding about its neurotoxicology.The present study exposed adult zebrafish to e...Methylparaben(MeP)is an emerging aquatic pollutant that is found to impact neural functions.However,it still lacks a comprehensive understanding about its neurotoxicology.The present study exposed adult zebrafish to environmentally realistic concentrations(0,1,3,and 10μg/L)of MeP for 28 days,with objectives to elucidate the neurotoxic effects andmechanisms.Proteomic profiling found that MeP pollutant induced distinct mechanism of neurotoxicity as a function of sex.MeP pollutant appeared to preferentially target the neurotransmission cascade via synapse junctions.In male brain,glutamatergic neural signaling was enhanced by 10μg/L of MeP in characteristics of higher glutamate neurotransmitter content(by 61.9%)and up-regulated glutamate receptor expression by 2.6-fold relative to the control.In MeP-exposed female brain,biomarker proteins of synapse formation and regeneration had significantly lower abundance,accounting for the blockage of synaptic neurotransmission.Furthermore,under the stress of MeP pollutant,both male and female zebrafish initiated a negative feedback mechanism along stress neuroendocrine axis by down-regulating the transcriptions of corticotropin-releasing hormone and its binding protein,which subsequently decreased blood cortisol concentrations.MeP subchronic exposure also disturbed innate immune function.In particular,significant increases in lipopolysaccharide(LPS)content by 15.6%were caused by MeP exposure in male brain,thereby inducing the synthesis of pro-inflammatory cytokines.In contrast,female brain was able to adaptively up-regulate the protein expression of blood brain barrier to inhibit the infiltration of LPS endotoxin into brain.Overall,the present findings pinpoint the potent neurotoxicity of MeP pollutant even at environmentally realistic concentrations.展开更多
In toxicological studies,experimental animals are generally subjected to dissection to obtain the tissues of concern,which causes great harm to the animals.In this regard,it is necessary to test and develop a non-inva...In toxicological studies,experimental animals are generally subjected to dissection to obtain the tissues of concern,which causes great harm to the animals.In this regard,it is necessary to test and develop a non-invasive strategy to prevent the animals from anthropic injury when achieving scientific objectives.Therefore,zebrafish fecal DNA and mR NA pools were assessed by using metagenomic and transcriptomic analyses based on their potential to diagnose toxicological impairment of polychlorinated biphenyl(PCB)126,a model persistent organic pollutant.The results showed that there was abundant zebrafish DNA and mR NA in the feces,which were,however,associated with contrasting profiles of physiological activities.As compared to DNA fragments,fecal mR NA provided a better representation of zebrafish physiological status.PCB126 exposure dramatically shifted the composition of fecal zebrafish DNA and m RNA as a function of sex.The differential m RNA caused by PCB126 clearly identified the toxicological fingerprint of PCB126.In summary,this study provides preliminary clues about the potential of fecal genes(mRNA in particular)in the development of non-invasive toxicological approaches.In the future,it is expected that more works will be conducted to screen sensitive diagnostic biomarkers from feces to increase the rate and reduce the cost of ecological risk assessment.展开更多
基金supported by the National Natural Science Foundation of China (Nos.22006159 and 31971236)the Research Grants Council Theme-Based Research Scheme (No.T21-602/16-R)+1 种基金the Natural Science Foundation of Hubei Province,China (No.2021CFA086)the State Key Laboratory of Freshwater Ecology and Biotechnology (No.2022FBZ02)。
文摘Perfluorobutanesulfonate(PFBS)is an emerging pollutant capable of potently disrupting the sex and thyroid endocrine systems of teleosts.However,the hypoxic and temporal variation in PFBS endocrine disrupting toxicity remain largely unknown.In the present study,adult marine medaka were exposed to environmentally realistic concentrations of PFBS(0 and 10μg/L)under normoxia or hypoxia conditions for 7 days,aiming to explore the interactive behavior between PFBS and hypoxia.In addition,PFBS singular exposure was extended till 21days under normoxia to elucidate the time-course progression in PFBS toxicity.The results showed that hypoxia inhibited the growth and caused the suspension of egg spawn regardless of PFBS exposure.With regard to the sex endocrine system,7-day PFBS exposure led to an acute stimulation of transcriptional profiles in females,which,subsequently,recovered after the 21-day exposure.The potency of hypoxia to disturb the sex hormones was much stronger than PFBS.A remarkable increase in estradiol concentration was noted in medaka blood after hypoxia exposure.Changes in sex endocrinology of coexposed fish were largely determined by hypoxia,which drove the formation of an estrogenic environment.PFBS further enhanced the endocrine disrupting effects of hypoxia.However,the hepatic synthesis of vitellogenin and choriogenin,two commonly used sensitive biomarkers of estrogenic activity,failed to initiate in response to the estrogen stimulus.Compared to sex endocrine system,disturbances in thyroidal axis by PFBS or hypoxia were relatively mild.Overall,the present findings will advance our toxicological understanding about PFBS pollutant under the interference of hypoxia.
基金supported by the National Natural Science Foundation of China(No.22006159)the Natural Science Foundation of Hubei Province,China(No.2021CFA086)the Innovative Team Program of Natural Science Foundation of Hubei Province,China(No.2021CFA032).
文摘To protect the wellbeing of research animals,certain non-invasive measures are in increasing need to facilitate an early diagnosis of health and toxicity.In this study,feces specimen was collected from adult zebrafish to profile the metabolome fingerprint.Variability in fecal metabolite composition was also distinguished as a result of aging,perfluorobutanesulfonate(PFBS)toxicant,and fecal transplantation.The results showed that zebrafish feces was very rich in a diversity of metabolites that belonged to several major classes,including lipid,amino acid,carbohydrate,vitamin,steroid hormone,and neurotransmitter.Fecal metabolites had functional implications to multiple physiological activities,which were characterized by the enrichment of digestion,absorption,endocrine,and neurotransmission processes.The high richness and functional involvement of fecal metabolites pinpointed feces as an abundant source of diagnostic markers.By comparison between young and aged zebrafish,fundamental modifications of fecal metabolomes were caused by aging progression,centering on the neuroactive ligand-receptor interaction pathway.Exposure of aged zebrafish to PFBS pollutant also significantly disrupted the metabolomic structure in feces.Of special concern were the changes in fecal hormone intermediates after PFBS exposure,which was concordant with the in vivo endocrine disrupting effects of PFBS.Furthermore,itwas intriguing that transplantation of young zebrafish feces efficientlymitigated the metabolic perturbation of PFBS in aged recipients,highlighting the health benefits of therapeutic strategies based on gut microbiota manipulation.In summary,the present study provides preliminary clues to evidence the non-invasive advantage of fecal metabolomics in the early diagnosis and prediction of physiology and toxicology.
基金supported by the National Natural Science Foundation of China(No.31971236)the Natural Science Foundation of Hubei Province,China(No.2021CFA086)the Innovative Team Program of Natural Science Foundation of Hubei Province,China(No.2021CFA032).
文摘Methylparaben(MeP)is an emerging aquatic pollutant that is found to impact neural functions.However,it still lacks a comprehensive understanding about its neurotoxicology.The present study exposed adult zebrafish to environmentally realistic concentrations(0,1,3,and 10μg/L)of MeP for 28 days,with objectives to elucidate the neurotoxic effects andmechanisms.Proteomic profiling found that MeP pollutant induced distinct mechanism of neurotoxicity as a function of sex.MeP pollutant appeared to preferentially target the neurotransmission cascade via synapse junctions.In male brain,glutamatergic neural signaling was enhanced by 10μg/L of MeP in characteristics of higher glutamate neurotransmitter content(by 61.9%)and up-regulated glutamate receptor expression by 2.6-fold relative to the control.In MeP-exposed female brain,biomarker proteins of synapse formation and regeneration had significantly lower abundance,accounting for the blockage of synaptic neurotransmission.Furthermore,under the stress of MeP pollutant,both male and female zebrafish initiated a negative feedback mechanism along stress neuroendocrine axis by down-regulating the transcriptions of corticotropin-releasing hormone and its binding protein,which subsequently decreased blood cortisol concentrations.MeP subchronic exposure also disturbed innate immune function.In particular,significant increases in lipopolysaccharide(LPS)content by 15.6%were caused by MeP exposure in male brain,thereby inducing the synthesis of pro-inflammatory cytokines.In contrast,female brain was able to adaptively up-regulate the protein expression of blood brain barrier to inhibit the infiltration of LPS endotoxin into brain.Overall,the present findings pinpoint the potent neurotoxicity of MeP pollutant even at environmentally realistic concentrations.
基金supported by the National Natural Science Foundation of China(No.31971236)the Knowledge Innovation Program of the Chinese Academy of Sciences+1 种基金the State Key Laboratory of Freshwater Ecology and Biotechnology(No.2019FBZ03)。
文摘In toxicological studies,experimental animals are generally subjected to dissection to obtain the tissues of concern,which causes great harm to the animals.In this regard,it is necessary to test and develop a non-invasive strategy to prevent the animals from anthropic injury when achieving scientific objectives.Therefore,zebrafish fecal DNA and mR NA pools were assessed by using metagenomic and transcriptomic analyses based on their potential to diagnose toxicological impairment of polychlorinated biphenyl(PCB)126,a model persistent organic pollutant.The results showed that there was abundant zebrafish DNA and mR NA in the feces,which were,however,associated with contrasting profiles of physiological activities.As compared to DNA fragments,fecal mR NA provided a better representation of zebrafish physiological status.PCB126 exposure dramatically shifted the composition of fecal zebrafish DNA and m RNA as a function of sex.The differential m RNA caused by PCB126 clearly identified the toxicological fingerprint of PCB126.In summary,this study provides preliminary clues about the potential of fecal genes(mRNA in particular)in the development of non-invasive toxicological approaches.In the future,it is expected that more works will be conducted to screen sensitive diagnostic biomarkers from feces to increase the rate and reduce the cost of ecological risk assessment.
