RESUMO
The novel brominated flame retardant, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), has increasingly been detected in environmental and biota samples. However, limited information is available regarding its toxicity, especially at environmentally relevant concentrations. In the present study, adult male zebrafish were exposed to varying concentrations of BTBPE (0, 0.01, 0.1, 1, and 10 µg/L) for 28 days. The results demonstrated underperformance in mating behavior and reproductive success of male zebrafish when paired with unexposed females. Additionally, a decline in sperm quality was confirmed in BTBPE-exposed male zebrafish, characterized by decreased total motility, decreased progressive motility, and increased morphological malformations. To elucidate the underlying mechanism, an integrated proteomic and phosphoproteomic analysis was performed, revealing a predominant impact on mitochondrial functions at the protein level and a universal response across different cellular compartments at the phosphorylation level. Ultrastructural damage, increased expression of apoptosis-inducing factor, and disordered respiratory chain confirmed the involvement of mitochondrial impairment in zebrafish testes. These findings not only provide valuable insights for future evaluations of the potential risks posed by BTBPE and similar chemicals but also underscore the need for further research into the impact of mitochondrial dysfunction on reproductive health.
Assuntos
Reprodução , Peixe-Zebra , Animais , Masculino , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Retardadores de Chama/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , FemininoRESUMO
Bis(2-ethylhexyl)-tetrabromophthalate (TBPH), a typical novel brominated flame retardant, has been ubiquitously identified in various environmental and biotic media. Consequently, there is an urgent need for precise risk assessment based on a comprehensive understanding of internal exposure and the corresponding toxic effects on specific tissues. In this study, we first investigated the toxicokinetic characteristics of TBPH in different tissues using the classical pseudo-first-order toxicokinetic model. We found that TBPH was prone to accumulate in the liver rather than in the gonad, brain, and muscle of both female and male zebrafish, highlighting a higher internal exposure risk for the liver. Furthermore, long-term exposure to TBPH at environmentally relevant concentrations led to increased visceral fat accumulation, signaling potential abnormal liver function. Hepatic transcriptome analysis predominantly implicated glycolipid metabolism pathways. However, alterations in the profile of associated genes and biochemical indicators revealed gender-specific responses following TBPH exposure. Besides, histopathological observations as well as the inflammatory response in the liver confirmed the development of nonalcoholic fatty liver disease, particularly in male zebrafish. Altogether, our findings highlight a higher internal exposure risk for the liver, enhancing our understanding of the gender-specific metabolic-disrupting potential associated with TBPH exposure.
Assuntos
Retardadores de Chama , Peixe-Zebra , Animais , Masculino , Feminino , Fígado/metabolismo , Metabolismo dos Lipídeos , Retardadores de Chama/toxicidade , Retardadores de Chama/análiseRESUMO
A novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant; hence, the knowledge of its long-term toxic effects and underlying mechanism would be critical for further health risk assessment. In the present study, the multi- and transgenerational toxicity of DBDPE was investigated in zebrafish upon a life cycle exposure at environmentally relevant concentrations. The significantly increased malformation rate and declined survival rate specifically occurred in unexposed F2 larvae suggested transgenerational development toxicity by DBDPE. The changing profiles revealed by transcriptome and DNA methylome confirmed an increased susceptibility in F2 larvae and figured out potential disruptions of glycolipid metabolism, mitochondrial energy metabolism, and neurodevelopment. The changes of biochemical indicators such as ATP production confirmed a disturbance in the energy metabolism, whereas the alterations of neurotransmitter contents and light-dark stimulated behavior provided further evidence for multi- and transgenerational neurotoxicity in zebrafish. Our findings also highlighted the necessity for considering the long-term impacts when evaluating the health of wild animals as well as human beings by emerging pollutants.
Assuntos
Poluentes Ambientais , Retardadores de Chama , Humanos , Animais , Peixe-Zebra , Larva , Bromobenzenos/toxicidade , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidadeRESUMO
Decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, is becoming increasingly prevalent in environmental and biota samples. While DBDPE has been shown to cause various biological adverse effects, the molecular mechanism behind these effects is still unclear. In this research, zebrafish embryos were exposed to DBDPE (50-400 µg/L) until 120 h post fertilization (hpf). The results confirmed the neurotoxicity by increased average swimming speed, interfered neurotransmitter contents, and transcription of neurodevelopment-related genes in zebrafish larvae. Metabolomics analysis revealed changes of metabolites primarily involved in glycolipid metabolism, oxidative phosphorylation, and oxidative stress, which were validated through the alterations of multiple biomarkers at various levels. We further evaluated the mitochondrial performance upon DBDPE exposure and found inhibited mitochondrial oxidative respiration accompanied by decreased mitochondrial respiratory chain complex activities, mitochondrial membrane potential, and ATP contents. However, addition of nicotinamide riboside could effectively restore DBDPE-induced mitochondrial impairments and resultant neurotoxicity, oxidative stress as well as glycolipid metabolism in zebrafish larvae. Taken together, our data suggest that mitochondrial dysfunction was involved in DBDPE-induced toxicity, providing novel insight into the toxic mechanisms of DBDPE as well as other emerging pollutants.
Assuntos
Retardadores de Chama , Peixe-Zebra , Animais , Larva , Bromobenzenos/farmacologia , Bromobenzenos/toxicidade , Retardadores de Chama/toxicidade , Mitocôndrias , Glicolipídeos/metabolismo , Glicolipídeos/farmacologiaRESUMO
Decabromodiphenyl ethane (DBDPE), a ubiquitous emerging pollutant, could be enriched in the liver of organisms, but its effects and mechanisms on liver development and regeneration remain largely unknown. In the present study, we first investigated the adverse effects on liver development and found decreased area and intensity of fluorescence in transgenic zebrafish larvae exposed to DBDPE; further results in wild-type zebrafish larvae revealed a possible mechanism involving disturbed MAPK/Fox O signaling pathways and cell cycle arrest as indicated by decreased transcription of growth arrest and DNA-damage-inducible beta a (gadd45ba). Subsequently, an obstructed recovery process of liver tissue after partial hepatectomy was characterized by the changing profiles of ventral lobe-to-intestine ratio in transgenic female adults upon DBDPE exposure; further results confirmed the adverse effects on liver regeneration by the alterations of the hepatic somatic index and proliferating cell nuclear antigen expression in wild-type female adults and also pointed out a potential role of a disturbed signaling pathway involving cell cycles and glycerolipid metabolism. Our results not only provided novel evidence for the hepatotoxicity and underlying mechanism of DBDPE but also were indicative of subsequent ecological and health risk assessment.
Assuntos
Retardadores de Chama , Peixe-Zebra , Animais , Feminino , Retardadores de Chama/toxicidade , Bromobenzenos/metabolismo , Bromobenzenos/toxicidade , Fígado/metabolismoRESUMO
Cadmium (Cd), a ubiquitous environmental hazardous heavy metal, poses a significant threat to the health of aquatic organisms, including teleosts. Although the toxic profile of Cd is well recognized, little is known regarding the overall view of toxic responses to varying aquatic environmental parameters (e.g., water hardness) at an individual level. Herein, differences in water hardness were partially mimicked by adjusting Ca2+ levels in E3 medium. As an in vivo model, zebrafish embryos were exposed to variable Ca2+ levels (NV, normal Ca2+; LV, low Ca2+; HV, high Ca2+) alone or combined with 30.7 µg/L Cd2+ (NC, LC, and HC, respectively) until 144 hr post-fertilization. The genome-wide transcriptome revealed differentially expressed genes between groups. Functional enrichment analysis found that biological processes related to metabolism, particularly lipid metabolism, were significantly disrupted in NC and LC treatments, while a remission was observed in the HC group. Biochemical assays confirmed that the decrease in Ca2+ enhanced synthesis, inhibited mobilization and increased the storage of lipids in Cd2+ treatments. This study suggests that the toxic effect of Cd on biological pathways will be influenced by Ca2+, which will improve the toxicological understanding and facilitate accurate assessment of Cd.
Assuntos
Cádmio , Poluentes Químicos da Água , Peixe-Zebra , Animais , Cádmio/toxicidade , Cádmio/metabolismo , Larva , Transcriptoma , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismoRESUMO
The novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a widespread environmental pollutant. However, the target tissue and toxicity of DBDPE are still not clear. In the current study, female zebrafish were exposed to 1 and 100 nM DBDPE for 28 days. Chemical analysis revealed that DBDPE tended to accumulate in the brain other than the liver and gonad. Subsequently, tandem mass tag-based quantitative proteomics and parallel reaction monitoring verification were performed to screen the differentially expressed proteins in the brain. Bioinformatics analysis revealed that DBDPE mainly affected the biological process related to muscle contraction and estrogenic response. Therefore, the neurotoxicity and reproductive disruptions were validated via multilevel toxicological endpoints. Specifically, locomotor behavioral changes proved the potency of neurotoxicity, which may be caused by disturbance of muscular proteins and calcium homeostasis; decreases of sex hormone levels and transcriptional changes of genes related to the hypothalamic-pituitary-gonad-liver axis confirmed reproductive disruptions upon DBDPE exposure. In summary, our results suggested that DBDPE primarily accumulated in the brain and evoked neurotoxicity and reproductive disruptions in female zebrafish. These findings can provide important clues for a further mechanism study and risk assessment of DBDPE.
Assuntos
Retardadores de Chama , Peixe-Zebra , Animais , Bromobenzenos/toxicidade , Sistema Endócrino , Monitoramento Ambiental , Feminino , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Contração MuscularRESUMO
In the current study, adult male zebrafish fed a normal diet (ND) or high-fat diet (HFD) were exposed to niclosamide (NIC) at environmentally relevant concentrations to reveal the accumulation and distribution in different tissues and evaluate the effects on liver-gut axis. Chemical analysis indicated that the liver bore a greater burden of NIC compared with the brain and gonads in adult zebrafish, and the HFD-fed fish bore greater burden in their liver and brain than those ND-fed fish. The indications from body weight, growth rate, body mass index, micro-CT images, biochemical and pathological changes confirmed that NIC can efficaciously curb weight gain and improve overloads of in plasma insulin and glucose in HFD-fed zebrafish. However, the potential effects on liver-gut axis in ND-fed zebrafish were also elucidated: NIC disturbed mitochondrial energy production, inhibited the glycemic and triacylglycerol biosynthesis but promoted triacylglycerol and free fatty acid catabolism, therefore reduced lipid accumulation in hepatocytes; NIC also impaired the physical barrier, evoked inflammatory and oxidative stress and led to microbiota dysbiosis in the intestine. There findings highlighted the necessity for evaluating its potential impacts on the health of wild animals as well as human beings upon long-term exposure.
Assuntos
Microbioma Gastrointestinal , Peixe-Zebra , Animais , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Niclosamida/metabolismo , Niclosamida/farmacologia , Triglicerídeos/metabolismo , Triglicerídeos/farmacologia , Peixe-Zebra/metabolismoRESUMO
Decabromodiphenyl ethane (DBDPE), a widely used novel brominated flame retardant, is gaining concerns due to rapidly increased contents in various environmental and biota samples. In the present study, zebrafish (Danio rerio) embryos were exposed to 2.91, 9.71, 29.14 and 97.12 µg/L of DBDPE until 120 h post-fertilization (hpf) to investigate the potential developmental neurotoxicity and underlying mechanisms. Chemical analysis revealed concentration-dependently increased body burdens of DBDPE in zebraï¬sh larvae, with bioaccumulation factors (BCFs) ranging from 414 to 726. Embryonic exposure to DBDPE caused hyperactivity without affecting the development of secondary motoneuron axons and muscle fibers. However, further results implicated that DBDPE may affect the locomotor regulatory network via different mechanisms at lower and higher concentrations. On the one hand, embryonic exposure to 2.91 µg/L DBDPE transiently promoted spontaneous coiling contractions, but showed no effects on touch-response and swimming activity in zebrafish larvae. The whole-body contents of neurotransmitters were significantly decreased. Significant decreased protein abundances of α1-TUBULIN and SYN2a and molecular docking results pointed out possible interactions of DBDPE with these two proteins. However, these changes may be unconcerned with the transient hyperactivity, and the exact molecular mechanisms need further investigation. On the other hand, 29.14 and 97.12 µg/L DBDPE exposure caused longer-lasting effects in promoting spontaneous coiling contractions, and also touch-response and swimming activity. At the same time, increased ACh contents (without changes of other neurotransmitters) and ChAT activity and inhibited transcription of nAChRs were observed at higher concentrations. Molecular docking indicated direct interaction of DBDPE with ChAT. The results suggested that DBDPE induced hyperactivity at higher concentrations was probably involved with disrupted cholinergic system, with ChAT as a potential target. Given that the body burden of DBDPE in lower concentration group was comparable with those detected in wild fish, the current results may provide useful information for ecological risk assessment.
Assuntos
Retardadores de Chama , Peixe-Zebra , Animais , Bromobenzenos , Colinérgicos/metabolismo , Colinérgicos/farmacologia , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Larva , Simulação de Acoplamento Molecular , Neurotransmissores/metabolismo , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/farmacologia , Peixe-Zebra/metabolismoRESUMO
The coexistence of nanoparticles and organic toxicants in the environment modifies pollutant bioavailability and toxicity. This study investigated the influence of silicon dioxide nanoparticles (n-SiO2) on the uptake of tetrabromobisphenol A (TBBPA) and its impact on the thyroid endocrine system in zebrafish larvae. Zebrafish (Danio rerio) embryos were exposed to TBBPA at different concentrations (50, 100, and 200 µg/L) alone or in combination with n-SiO2 (25 mg/L) until 120 h post-fertilization (hpf). Chemical measurements showed that both TBBPA and n-SiO2 were bioconcentrated in zebrafish larvae, and the uptake of TBBPA was enhanced by n-SiO2. Furthermore, zebrafish larvae exposed to 200 µg/L TBBPA alone exhibited significantly increased T4 contents and decreased T3 contents, whereas n-SiO2 treatment alone did not have a detectable effect. Furthermore, the thyroid hormone levels changed more upon treatment with 200 µg/L TBBPA combined with 25 mg/L n-SiO2 than upon TBBPA treatment alone. Alterations in gene transcription along the related hypothalamic-pituitary-thyroid (HPT) axis were observed, and expression of the binding and transport protein transthyretin (TTR) was significantly decreased for both TBBPA alone and co-exposure with n-SiO2. Thus, the current study demonstrates that n-SiO2, even at the nontoxic concentrations, increases thyroid hormone disruption in zebrafish larvae co-exposed to TBBPA by promoting its bioaccumulation and bioavailability.
Assuntos
Nanopartículas/toxicidade , Bifenil Polibromatos/metabolismo , Dióxido de Silício/toxicidade , Poluentes Químicos da Água/metabolismo , Animais , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Larva/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Peixe-Zebra/fisiologiaRESUMO
Bisphenol S (BPS) is an alternative chemical to bisphenol A commonly used in food packaging materials. It raises concerns due to potential adverse effects on human health. However, limited evidence exists regarding reproductive toxicity from BPS exposure, and the mechanism of associated transgenerational toxicity remains unclear. In this study, pregnant SD rats were exposed to two different doses of BPS (0.05 or 20 mg/kg) from GD6 to PND21. The objective was to investigate reproductive and transmissible toxicity induced by BPS, explore endocrine effects, and uncover potential underlying mechanisms in rats. Perinatal exposure to BPS in the F0 generation significantly decreased the rate of body weight, ovarian organ coefficient, and growth and development of the F1 generation. Notably, these changes included abnormal increases in body weight and length, estrous cycle disruption, and embryonic dysplasia in F1. 4D-DIA proteomic and PRM analyses revealed that exposure to 20 mg/kg group significantly altered the expression of proteins, such as Lhcgr and Akr1c3, within the steroid biosynthetic pathway. This led to elevated levels of FSH and LH in the blood. The hypothalamic-pituitary-ovarian (HPO) axis, responsible for promoting fertility through the cyclic secretion of gonadotropins and steroid hormones, was affected. RT-qPCR and Western blot results demonstrated that the expression of GnRH in the hypothalamus was decreased, the GnRHR in the pituitary gland was decreased, and the expression of FSHß and LHß in the pituitary gland was increased. Overall, BPS exposure disrupts the HPO axis, hormone levels, and steroid biosynthesis in the ovaries, affecting offspring development and fertility. This study provides new insights into the potential effects of BPS exposure on the reproductive function of the body and its relevant mechanisms of action.
Assuntos
Disruptores Endócrinos , Fenóis , Ratos Sprague-Dawley , Reprodução , Sulfonas , Animais , Feminino , Fenóis/toxicidade , Ratos , Gravidez , Sulfonas/toxicidade , Reprodução/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Ovário/efeitos dos fármacosRESUMO
Because of its ubiquitous occurrence in the environment, decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, has been widely concerned. However, its transgenerational thyroid disrupting potential and intricate mechanism are barely explored. Therefore, zebrafish embryos were exposed to environmentally relevant concentrations of DBDPE (0, 0.1, 1 and 10 nM) until sexual maturity. The results indicated that life-time exposure to DBDPE caused anxiety-like behavior in unexposed offspring. Furthermore, the changing of thyroid hormones as well as transcriptional and DNA methylation level in the promoter region of related genes were evaluated. The thyroid disruptions observed in F1 larvae were primarily attributed to excessive transfer of thyroid hormone from F0 adults to F1 eggs. Conversely, the disruptions in F2 larvae were likely due to inherited epigenetic changes, specifically hypomethylation of crh and hypermethylation of ugt1ab, passed down from the F1 generation. Additionally, our results revealed sex-specific responses of the hypothalamic-pituitary-thyroid (HPT) axis in adult zebrafish. Furthermore, thyroid disruptions observed in unexposed offspring were more likely inherited from their mothers. The current results prompted our in-depth understanding of the multi- and transgenerational toxicity by DBDPE, and also highlighted the need to consider their adverse effects on persistent and inheritable epigenetic changes in future research on emerging pollutants.
Assuntos
Bromobenzenos , Epigênese Genética , Retardadores de Chama , Glândula Tireoide , Peixe-Zebra , Animais , Glândula Tireoide/efeitos dos fármacos , Retardadores de Chama/toxicidade , Bromobenzenos/toxicidade , Disruptores Endócrinos/toxicidade , Metilação de DNA/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Hormônios Tireóideos/metabolismo , Sistema Endócrino/efeitos dos fármacos , Feminino , MasculinoRESUMO
The bioavailability and toxicity of organic pollutants in aquatic organisms can be largely affected by the co-existed nanoparticles. However, the impacts of such combined exposure on the visual system remain largely unknown. Here, we systematically investigated the visual toxicity in zebrafish larvae after single or joint exposure to titanium dioxide nanoparticles (n-TiO2) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) at environmentally relevant levels. Molecular dynamics simulations revealed the enhanced transmembrane capability of the complex than the individual, which accounted for the increased bioavailability of both TBPH and n-TiO2 when combined exposure to zebrafish. Transcriptome analysis showed that co-exposure to n-TiO2 and TBPH interfered with molecular pathways related to eye lens structure and sensory perception of zebrafish. Particularly, n-TiO2 or TBPH significantly suppressed the expression of ßB1-crystallin and rhodopsin in zebrafish retina and lens, which was further enhanced after co-exposure. Moreover, we detected disorganized retinal histology, stunted lens development and significant visual behavioral changes of zebrafish under co-exposure condition. The overall results suggest that combined exposure to water borne n-TiO2 and TBPH increased their bioavailability, resulted in severer damage to optic nerve development and ultimately abnormal visual behavior patterns, highlighting the higher potential health risks of co-exposure to aquatic vertebrates.
Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Peixe-Zebra/fisiologia , Larva/metabolismo , Nanopartículas/toxicidade , Titânio/toxicidade , Titânio/metabolismo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
Previous studies have shown the harmful effects of nanoscale particles on the intestinal tracts of organisms. However, the specific mechanisms remain unclear. Our present study focused on examining the uptake and distribution of polystyrene nanoplastics (PS-NPs) in zebrafish larvae, as well as its toxic effects on the intestine. It was found that PS-NPs, marked with red fluorescence, primarily accumulated in the intestine section. Subsequently, zebrafish larvae were exposed to normal PS-NPs (0.2-25 mg/L) over a critical 10-day period for intestinal development. Histopathological analysis demonstrated that PS-NPs caused structural changes in the intestine, resulting in inflammation and oxidative stress. Additionally, PS-NPs disrupted the composition of the intestinal microbiota, leading to alterations in the abundance of bacterial genera such as Pseudomonas and Aeromonas, which are associated with intestinal inflammation. Metabolomics analysis showed alterations in metabolites that are primarily involved in glycolipid metabolism. Furthermore, MetOrigin analysis showed a significant correlation between bacterial flora (Pedobacter and Bacillus) and metabolites (D-Glycerate 2-phosphate and D-Glyceraldehyde 3-phosphate), which are related to the glycolysis/gluconeogenesis pathways. These findings were further validated through alterations in multiple biomarkers at various levels. Collectively, our data suggest that PS-NPs may impair the intestinal health, disrupt the intestinal microbiota, and subsequently cause metabolic disorders.
Assuntos
Microbioma Gastrointestinal , Glicolipídeos , Larva , Poliestirenos , Peixe-Zebra , Animais , Poliestirenos/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Glicolipídeos/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Nanopartículas/toxicidade , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Microplásticos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidadeRESUMO
Polypropylene microplastics (PP-MPs) are emerging pollutant commonly detected in various environmental matrices and organisms, while their adverse effects and mechanisms are not well known. Here, zebrafish embryos were exposed to environmentally relevant concentrations of PP-MPs (0.08-50 mg/L) from 2 h post-fertilization (hpf) until 120 hpf. The results showed that the body weight was increased at 2 mg/L, heart rate was reduced at 0.08 and 10 mg/L, and behaviors were impaired at 0.4, 10 or 50 mg/L. Subsequently, transcriptomic analysis in the 0.4 and 50 mg/L PP-MPs treatment groups indicated potential inhibition on the glycolysis/gluconeogenesis and oxidative phosphorylation pathways. These findings were validated through alterations in multiple biomarkers related to glucose metabolism. Moreover, abnormal mitochondrial ultrastructures were observed in the intestine and liver in 0.4 and 50 mg/L PP-MPs treatment groups, accompanied by significant decreases in the activities of four mitochondrial electron transport chain complexes and ATP contents. Oxidative stress was also induced, as indicated by significantly increased ROS levels and significant reduced activities of CAT and SOD and GSH contents. All the results suggested that environmentally relevant concentrations of PP-MPs could induce disrupted mitochondrial energy metabolism in zebrafish, which may be associated with the observed behavioral impairments. This study will provide novel insights into PP-MPs-induced adverse effects and highlight need for further research.
Assuntos
Metabolismo Energético , Microplásticos , Mitocôndrias , Polipropilenos , Poluentes Químicos da Água , Peixe-Zebra , Animais , Poluentes Químicos da Água/toxicidade , Metabolismo Energético/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Microplásticos/toxicidade , Polipropilenos/toxicidade , Larva/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacosRESUMO
Progestins are worldwide environmental contaminants, however, their ecotoxicological risks and underlying molecular mechanisms of effects are not fully understood. In this study, newly hatched rare minnow (Gobiocypris rarus) larvae were exposed to environmentally realistic concentrations (1 and 10 ng/L) of levonorgestrel (LNG) for 6 months. The sex ratios were not affected by LNG at both concentrations, but the growth was significantly inhibited at 10 ng/L while promoted at 1 ng/L. Histological analysis revealed impaired gonadal development. Plasma concentrations of estradiol in females and testosterone in both sexes were significantly induced after exposure to 1 ng/L LNG; plasma concentrations of 11-ketotestosterone were markedly increased in females exposed to 10 ng/L LNG and in males exposed to both concentrations of LNG. The transcription of cyp19a1a was significantly up-regulated in ovaries exposed to LNG at both concentrations, while cyp17a1 was down-regulated in testes exposed to 10 ng/L LNG. The global DNA methylation level was significantly decreased in testes exposed to 10 ng/L LNG, which might be associated with inhibited spermatogenesis. Gender-specific changes in CpG methylation patterns were induced by LNG in the 5' flanking region of cyp19a1a, with hypomethylation in ovaries but hypermethylation in testes, which was linked to the regulation of cyp19a1a transcription. The results suggest that LNG could induce endocrine disrupting effects in fish at environmentally realistic concentrations, which may be linked to altered DNA methylation. This study indicates potentially high ecological risk of LNG to fish populations, and warrants researches on regulatory mechanisms of epigenetic modifications in progestin-induced effects.
Assuntos
Cyprinidae , Levanogestrel , Animais , Cyprinidae/fisiologia , Metilação de DNA , Feminino , Gônadas , Levanogestrel/metabolismo , Levanogestrel/toxicidade , Masculino , OvárioRESUMO
Silicon dioxide nanoparticles (n-SiO2) absorb tetrabromobisphenol A (TBBPA) and modify its bioavailability and toxicity in the aquatic phase; embryonic chorion is an efficient barrier against nanoparticles (e.g., SiO2) and influences their toxicity. However, few studies have investigated developmental neurotoxicity in fish after co-exposure to TBBPA and n-SiO2, especially considering the barrier function of the chorion. In the present study, zebrafish embryos were exposed to TBBPA (50, 100, and 200 µg/L) alone or in combination with n-SiO2 (25 mg/L) until 24 or 120 h post fertilization (hpf), in the presence and absence of the chorion. The results confirmed that TBBPA exposure alone significantly downregulated the expression of neurodevelopment marker genes (mbp, alpha-tubulin, shha, and gfap), altered acetylcholinesterase activity and acetylcholine content, and affected locomotor behavior at different developmental stages. Moreover, the results indicated that n-SiO2 promoted TBBPA-induced neurotoxic effects in zebrafish larvae at 120 hpf, including further repression of the transcription of CNS-related genes, disruption of the cholinergic system, and decrease in the average swimming speed under dark/light stimulation. However, scanning electron microscopy/energy dispersive spectroscopy analysis revealed that at 24 hpf, the embryonic chorion efficiently blocked n-SiO2 and consequently decreased the bioaccumulation of TBBPA and TBBPA-induced neurotoxicity in dechorionated zebrafish embryos. Taken together, the results demonstrate that n-SiO2 affected the bioavailability and neurodevelopmental toxicity of TBBPA, and their combined toxicity to zebrafish embryos was mitigated by embryonic chorion, which will facilitate risk assessment on n-SiO2 and TBBPA and improve understanding the function of the fish embryonic chorion.
Assuntos
Nanopartículas , Peixe-Zebra , Acetilcolinesterase/metabolismo , Animais , Córion , Embrião não Mamífero , Larva , Nanopartículas/toxicidade , Bifenil Polibromatos , Dióxido de Silício/toxicidadeRESUMO
Deltamethrin, a widely used type II pyrethroid insecticide, was reported with neurotoxicity to aquatic organisms, such as fish. However, the effects and potential mechanisms on the central nervous system remain largely unknown, especially under environmental concentrations. Therefore, we exposed adult female zebrafish to environmentally relevant levels of deltamethrin (30, 100, and 333 ng/L) for 21 days to assess neurobehavioral changes related to the central nervous system and explore the modes of action. Behavioral assays revealed significant increases in the swimming speeds, residence time near other fish and the shoaling cohesion in exposed fish. Transcriptomic results enriched the disrupted neural functions involving the glutamatergic and dopaminergic synapses in the brain. The qRT-PCR confirmed the upregulation of the factors for promoting the glutamate release. The measurement of neurotransmitters showed significantly increased content of the excitatory neurotransmitter glutamate in the brain. Taken together, deltamethrin exposure increased the glutamate level and promoted the release of such an excitatory neurotransmitter between the glutamatergic synapses in the brain, which eventually led to hyperactivity of social behaviors in adult zebrafish.
Assuntos
Piretrinas , Peixe-Zebra , Animais , Feminino , Nitrilas/toxicidade , Piretrinas/toxicidade , Natação , Peixe-Zebra/fisiologiaRESUMO
Niclosamide (NIC) is the most widely used molluscicides for preventing the occurrence of schistosomiasis disease, and its residues can be found in various environmental samples. However, the toxicity mechanism of NIC during early developmental stage remains largely unknown. In the present study, zebrafish embryos were acutely exposed to NIC at an environmentally realistic concentration (0 and 40 µg/L) until 120 h post-fertilization. Transcriptomic sequencing was performed to provide mechanistic insight into developmental impairment. Pathway enrichment analyses found that biological processes related to lipid metabolism were significantly affected in exposed zebrafish larvae. Consistently, biochemical measurements showed that NIC developmental exposure depleted lipid storage, elevated lipid utilization, but inhibited lipid synthesis. Furthermore, as characterized by pathway enrichment and hormonal levels, steroid hormone biosynthesis was also significantly disrupted by NIC exposure in zebrafish larvae, indicating the endocrine disrupting potential of NIC. Detoxifying phase I and II processes (e.g., metabolism, conjugation and elimination) were significantly activated by NIC exposure. Overall, our findings suggest that NIC developmental exposure at an environmentally realistic concentration disturbs the lipid metabolism, induces endocrine disruption and initiates detoxifying capacity in zebrafish larvae, which will provide preliminary clues for developmental toxicity mechanisms of NIC.
Assuntos
Anticestoides/toxicidade , Disruptores Endócrinos/toxicidade , Niclosamida/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Embrião não Mamífero/efeitos dos fármacos , Larva/metabolismo , Transcriptoma , Peixe-Zebra/metabolismoRESUMO
Nanoparticle such as silicon dioxide nanoparticles (nano-SiO2) are extensively produced and applied in society. Hence there is an increasing concern about their exposure and toxicity to human and wildlife. To understand the effects of sizes of NPs on their bioavailability and toxicity, zebrafish (Danio rerio) embryos (2â¯h post-fertilization, hpf) were exposed to 25, 50 and 100â¯mg/L of 15 or 30â¯nm nano-SiO2 for 5 days respectively. The results showed that SiO2 could be readily uptaken by zebrafish, and the accumulation of SiO2 was significantly higher in 15â¯nm treatments groups compared to 30â¯nm nano-SiO2 treated groups. Furthermore, exposure to 15â¯nm nano-SiO2 at the concentration of 100â¯mg/L resulted in more significant changes in reactive oxygen species (ROS) levels, perturbation of lipid peroxidative and antioxidant system than the same concentration of 30â¯nm nano-SiO2, indicating small sized nano-SiO2 evoked severer oxidative stress in zebrafish larvae. In addition, the more significant up-regulation of transcription of genes related to oxidative stress (e.g., nrf2 and sod1) in 15â¯nm nano-SiO2 at the 100â¯mg/L treatments groups provided more evidence for this speculation. Given the above, 15â¯nm nano-SiO2 were more likely to enter and accumulate in zebrafish larvae, thus causing more serious oxidative stress in vivo. These results may provide additional information on the fate and toxicities of different sizes of NPs.