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Biodegradable plastics have been commonly developed and applied as an alternative to traditional plastics, which cause environmental plastic pollution. However, biodegradable plastics still present limitations such as stringent degradation conditions and slow degradation rate, and may cause harm to the environment and organisms. Consequently, in this study, zebrafish was used to evaluate the effects of five biodegradable microplastics (MPs), polyglycolic acid (PGA), polylactic acid (PLA), polybutylene succinate (PBS), polyhydroxyalkanoate (PHA) and polybutylene adipate terephthalate (PBAT) exposure on the early development, retina morphology, visually-mediated behavior, and thyroid signaling at concentrations of 1 mg/L and 100 mg/L. The results indicated that all MPs induced decreased survival rate, reduced body length, smaller eyes, and smaller heads, affecting the early development of zebrafish larvae. Moreover, the thickness of retinal layers, including inner plexiform layer (IPL), outer nuclear layer (ONL), and retinal ganglion layer (RGL) was decreased, and the expression of key genes related to eye and retinal development was abnormally altered after all MPs exposure. Exposure to PBS and PBAT led to abnormal visually-mediated behavior, indicating likely affected the visual function. All MPs could also cause thyroid system disorders, among which alterations in the thyroid hormone receptors (TRs) genes could affect the retinal development of zebrafish larvae. In summary, biodegradable MPs exhibited eye developmental toxicity and likely impaired the visual function in zebrafish larvae. This provided new evidence for revealing the effects of biodegradable plastics on aquatic organism development and environmental risks to aquatic ecosystems.
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Zebrafish are considered as model organisms in biological and medical research because of their high degree of homology with human genes. Automatic behavioral analysis of multiple zebrafish based on visual tracking is expected to improve research efficiency. However, vision-based multi-object tracking algorithms often suffer from data loss owing to mutual occlusion. In addition, simply tracking zebrafish as points is not sufficient-more detailed information, which is required for research on zebrafish behavior. In this paper, we propose Zebrafishtracker3D, which utilizes a skeleton stability strategy to reduce detection error caused by frequent overlapping of multiple zebrafish effectively and estimates zebrafish skeletons using head coordinates in the top view. Further, we transform the front- and top-view matching task into an optimization problem and propose a particle-matching method to perform 3D tracking. The robustness of the algorithm with respect to occlusion is estimated on the dataset comprising two and three zebrafish. Experimental results demonstrate that the proposed algorithm exhibits a multiple object tracking accuracy (MOTA) exceeding 90% in the top view and a 3D tracking matching accuracy exceeding 90% in the complex videos with frequent overlapping. It is noteworthy that each instance in the trace saves its skeleton. In addition, Zebrafishtracker3D is applied in the zebrafish courtship experiment, establishes the stability of the method in applications of life science, and proves that the data can be used for behavioral analysis. Zebrafishtracker3D is the first algorithm that realizes 3D skeleton tracking of multiple zebrafish simultaneously.
Assuntos
Algoritmos , Comportamento Animal , Imageamento Tridimensional , Peixe-Zebra , Animais , Imageamento Tridimensional/métodos , Gravação em Vídeo/métodosRESUMO
Increasing evidence indicates that disturbance of the clock genes, which leads to systemic endocrine perturbation, plays a crucial role in the pathogenesis of metabolic and liver diseases. Fluorene-9-bisphenol (BHPF) is utilized in the manufacturing of plastic materials but its biological effects on liver homeostasis remain unknown. The impacts and involved mechanisms of BHPF on the liver diseases, metabolism, and circadian clock were comprehensively studied by zebrafish and mouse models. The therapeutic effect of melatonin (MT) was also verified. Zebrafish and mouse models with either acute exposure (0.5 and 1 µmol/L, 1-4 days post-fertilization) or chronic oral exposure (0.5 and 50 mg/(kg·2 days), 30 days) were established with various BHPF concentrations. Herein, we identified a crucial role for estrogenic regulation in liver development and circadian locomotor rhythms damaged by BHPF in a zebrafish model. BHPF mice showed chaos in circadian activity through the imbalance of circadian clock component Brain and Muscle Aryl hydrocarbon receptor nuclear translocator-like 1 in the liver and brain. The liver sexual dimorphic alteration along with reduced growth hormone and estrogens played a critical role in damaged glucose metabolism, hepatic inflammation, and fibrosis induced by BHPF. Besides, sleep improvement by exogenous MT alleviated BHPF-related glucose metabolism and liver injury in mice. We proposed the pathogenesis of metabolic and liver disease resulting from BHPF and promising targeted therapy for liver metabolism disorders associated with endocrine perturbation chemicals. These results might play a warning role in the administration of endocrine-disrupting chemicals in everyday life and various industry applications.
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Ritmo Circadiano , Fluorenos , Peixe-Zebra , Animais , Camundongos , Fluorenos/toxicidade , Ritmo Circadiano/efeitos dos fármacos , Hepatopatias/tratamento farmacológico , Fenóis/toxicidadeRESUMO
Previous studies have identified the exposure to ubiquitous environmental endocrine disruptors may be a risk factor of neurological disorders. However, the effects of fluorene-9-bisphenol (BHPF) in environmental exposure concentrations associated with these disorders are poorly understood. In this study, classic light-dark and social behavior tests were performed on zebrafish larvae and adults exposed BHPF exposure to evaluate social behavioral disorders and the microbiota-gut-brain axis was assessed to reveal the potential mechanisms underlying the behavioral abnormalities observed. Our results demonstrated that zebrafish larvae exposed to an environmentally relevant concentration (0.1 nM) of BHPF for 7 days showed a diminished response to external environmental factors (light or dark). Zebrafish larvae exposed to BHPF for 7 days or adults exposed to BHPF for 30 days at 1 µM displayed significant behavioral inhibition and altered social behaviors, including social recognition, social preference, and social fear contagion, indicating autism-like behaviors were induced by the exposure. BHPF exposure reduced the distribution of Nissl bodies in midbrain neurons and significantly reduced 5-hydroxytryptamine signaling. Oxytocin (OXT) levels and expression of its receptor oxtra in the gut and brain were down-regulated by BHPF exposure. In addition, the expression levels of genes related to the excitation-inhibitory balance of synaptic transmission changed. Microbiomics revealed increased community diversity and altered abundance of some microflora, such as an elevation in Bacillota and Bacteroidota and a decline in Mycoplasmatota in zebrafish guts, which might contribute to the abnormal neural circuits and autism-like behaviors induced by BHPF. Finally, the rescue effect of exogenous OXT on social behavioral defects induced by BHPF exposure was verified in zebrafish, highlighting the crucial role of OXT signaling through gut-brain axis in the regulatory mechanisms of social behaviors affected by BHPF. This study contributes to understanding the effects of environmental BHPF exposure on neuropsychiatric disorders and attracts public attention to the health risks posed by chemicals in aquatic organisms. The potential mental disorders should be considered in the safety assessments of environmental pollutants.
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Eixo Encéfalo-Intestino , Fluorenos , Ocitocina , Comportamento Social , Peixe-Zebra , Animais , Fluorenos/toxicidade , Ocitocina/metabolismo , Eixo Encéfalo-Intestino/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Poluentes Químicos da Água/toxicidade , Comportamento Animal/efeitos dos fármacos , Larva/efeitos dos fármacos , Fenóis/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
BACKGROUND: The widespread use of sodium propionate as a preservative in food may affect public health. We aimed to assess the effects of sodium propionate on circadian rhythms and pancreatic development in zebrafish and the possible underlying mechanisms. RESULTS: In this experiment, we analyzed the relationship between circadian rhythms and pancreatic development and then revealed the role of the thyroid endocrine system in zebrafish. The results showed that sodium propionate interfered with the rhythmic behavior of zebrafish, and altered the expression of important rhythmic genes. Experimental data revealed that pancreatic morphology and developmental genes were altered after sodium propionate exposure. Additionally, thyroid hormone levels and key gene expression associated with the hypothalamic-pituitary-thyroid axis were significantly altered. Melatonin at a concentration of 1 µmol L-1, with a mild effect on zebrafish, observably alleviated sodium propionate-induced disturbances in circadian rhythms and pancreatic development, as well as regulating the thyroid system. CONCLUSION: Melatonin, while modulating the thyroid system, significantly alleviates sodium propionate-induced circadian rhythm disturbances and pancreatic developmental disorders. We further revealed the deleterious effects of sodium propionate as well as the potential therapeutic effects of melatonin on circadian rhythm, pancreatic development and the thyroid system. © 2024 Society of Chemical Industry.
Assuntos
Ritmo Circadiano , Sistema Hipotálamo-Hipofisário , Melatonina , Pâncreas , Propionatos , Glândula Tireoide , Peixe-Zebra , Animais , Melatonina/farmacologia , Peixe-Zebra/crescimento & desenvolvimento , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Hormônios Tireóideos/metabolismoRESUMO
Fluorene-9-bisphenol (BHPF) is widely used in the manufacture of plastic products and potentially disrupts several physiological processes, but its biological effects on social behavior remain unknown. In this study, we investigated the effects of BHPF exposure on anxiety-like and social behavior in female mice and the potential mechanisms, thereby proposing a potential therapy strategy. We exposed female Balb/c mice to BHPF by oral gavage at different doses (0.5, 50 mg/kg bw/2-day) for 28 days, which were found BHPF (50 mg/kg) exposure affected motor activity in the open field test (OFT) and elevated cross maze (EPM), resulting in anxiety-like behaviors, as well as abnormal social behavioral deficits in the Social Interaction Test (SIT). Analysis of histopathological staining results showed that BHPF exposure caused damage to hippocampal neurons in the CA1/CA3/DG region and decreased Nissl pyramidal neurons in the CA1/CA3 regions of the hippocampus, as well as a decrease in parvalbumin neuron expression. In addition, BHPF exposure upregulated the expression of excitatory and inhibitory (E/I) vesicle transporter genes (Vglut1, Vglut2, VGAT, GAD67, Gabra) and axon growth gene (Dcc) in the mouse hippocampus. Interestingly, behavioral disturbances and E/I balance could be alleviated by exogenous melatonin (15 mg/kg bw/2-day) therapy. Our findings suggest that exogenous melatonin may be a potential therapy with protective potential for ameliorating or preventing BHPF-induced hippocampal neuronal damage and behavioral disturbances. This study provided new insight into the neurotoxicological effects on organisms exposed to endocrine-disrupting chemicals and aroused our vigilance in current environmental safety about chemical use.
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Ansiedade , Fluorenos , Melatonina , Camundongos Endogâmicos BALB C , Comportamento Social , Animais , Camundongos , Ansiedade/induzido quimicamente , Feminino , Fluorenos/toxicidade , Melatonina/farmacologia , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Fenóis/toxicidadeRESUMO
The increasing side effects of traditional medications used to treat type II diabetes have made research into the development of safer and more effective natural medications necessary. ACT001, a derivative of parthenolide, has been shown to have good anti-inflammatory and antitumor effects; however, its role in diabetes is unclear. The short-chain fatty acid propionate is a common food preservative that has been found to cause disturbances in glucose metabolism in mice and humans. This study aimed to investigate whether sodium propionate could aggravate insulin resistance in obese mice and cause diabetes and to study the alleviative effects and potential mechanisms of action of ACT001 on insulin resistance in diabetic mice. Type II diabetic mice were adminietered sodium propionate combined with a high-fat diet (HFD + propionate) by gavage daily for four weeks. Biochemical analysis showed that ACT001 significantly affected blood glucose concentration in diabetic mice, mainly by downregulating the expression of phosphoenolpyruvate carboxykinase 2 and glucose-6-phosphatase. Meanwhile, the level of fatty acid-binding protein 4 in the liver was significantly decreased. ACT001 has a protective effect on the liver and adipose tissue of mice. In addition, the results of the running wheel experiment indicated that ACT001 alleviated the circadian rhythm disorder caused by insulin resistance to a certain extent. This study revealed the potential mechanism by which ACT001 alleviates insulin resistance and provides ideas for developing natural antidiabetic drugs.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Furanos , Resistência à Insulina , Sesquiterpenos , Humanos , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Propionatos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Camundongos Endogâmicos C57BL , Insulina/metabolismoRESUMO
Polyglycolic acid (PGA) is an emerging biodegradable plastic material. Together with polylactic acid (PLA), PGA is considered a suitable alternative to conventional plastics and has been widely used in biomedical and food packaging industries. However, degradable plastics continue to face the drawbacks of harsh degradation environment and long degradation time, and may harm the environment and the human body. Therefore, our study focused on assessing the effects of degradable microplastics PGA and PLA on the development and neurobehavior of zebrafish. The results showed that PGA and PLA had little effect on 3-10 hpf embryos. However, developmental stunting was observed in a100 mg/L PGA and PLA-exposed group at 24 hpf. In addition, PGA and PLA exposure decreased the survival and hatching rates, increased wakefulness, and reduced sleep in zebrafish. This indicates that PGA and PLA may affect the circadian behavior of zebrafish by affecting the brain-derived neurotrophic factor (BDNF). Therefore, our results suggest that PGA and PLA exposure induces developmental toxicity, reduces voluntary locomotion, induces of anxiety-like behaviors, and impairs sleep/wake behaviors in zebrafish larvae. This also suggests that the potentially toxic effects of degradable plastics cannot be ignored and that the biological effects of PGA require further research.
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Plásticos , Poluentes Químicos da Água , Animais , Humanos , Plásticos/toxicidade , Microplásticos , Peixe-Zebra , Poliésteres/toxicidade , Ritmo Circadiano , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Ácido PoliglicólicoRESUMO
Corannulene (Cor), a special carbon material, evidenced strong protein binding capacity which regulating lysozyme crystallization and controlling reactive oxygen species (ROS) generation. Ion channel protein play role in regulating ion channel functions to affect physiological functions. However, the interaction between Cor and ion channel protein have not been studied. In this study, PEG/Cor nanoparticles (PEG/Cor Nps) were prepared by mPEG-DSPE. The PEG/Cor Nps localized in cytoplasm and produced cytotoxicity at high concentration. Whole cell patch clamp examined ion channel functions after incubate PEG/Cor Nps with PC-12 cell. we found that PEG/Cor Nps inhibited voltage-gated Na+ ion channels in a dose- and time-dependent manner but not act on voltage-gated K+ ion channels. The potential mechanisms were revealed by all-atom molecular dynamic (MD) simulations. The results showed that PEG/Cor Nps block the pore of sodium ion channel protein due to dose- and time-dependent accumulation. Besides, the orientation angle (θ) configuration of PEG/Cor Nps will be inverted with the accumulation to generate two blocking mechanisms. Different from other carbon nanomaterials, the blockage mechanism of PEG/Cor Nps provides novel insights into the mechanisms of interaction between carbon nanomaterials and protein.
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Hidrocarbonetos Policíclicos Aromáticos , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Sódio Disparados por Voltagem , Ligação ProteicaRESUMO
In vertebrates, the behavior of congenital sex differences between males and females is highly dependent on steroid signals and hormonal milieu. The presence of endocrine disrupting chemicals (EDCs) in the environment generally plays a similar role to sex hormones, so its interference with aquatic organism population stability can not be ignored and is worth studying. Fluorene-9-bisphenol (BHPF) has been clarified as an endocrine disruptor on organisms by several studies but its mechanism in perturbation of courtship behavior of female zebrafish is not clear. Here, we proposed an automated multi-zebrafish tracking method quantifying the courtship process and reported that zebrafish females exposed to BHPF, are not receptive to males but rather court females, and lose normal ovarian function with an altered sex steroid milieu. Our results showed that BHPF damaged 17ß-estradiol synthesis by down-regulation of sox3 and cyp19a1a, linking apoptosis with ovary development and female fecundity. The down-regulated expression of estrogen signaling through an estrogen receptor, esr2b, caused the induction of masculinization of female courtship behavior and sexual preference in zebrafish females after BHPF treatment. This process might be mediated by inhibiting the transcription of a neuropeptide B (npb) in the brain. Our study reveals that the estrogen signaling pathway may play an important role in classical courtship behavior and sexual preference of zebrafish. This study provided evidence that anti-estrogenic chemical exposure caused adverse effects on the regulation of the brain-gonad-estrogen axis of aquatic organisms, which should be of concern and highlighted the importance of controlling environmental contamination.
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Disruptores Endócrinos , Poluentes Químicos da Água , Animais , Feminino , Masculino , Peixe-Zebra/metabolismo , Corte , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo , Disruptores Endócrinos/toxicidade , Disruptores Endócrinos/metabolismo , Estrogênios/metabolismo , Estradiol/metabolismo , Hormônios Esteroides Gonadais/metabolismoRESUMO
Thyroid hormone has a variety of physiological functions and plays an important role in the development of central nervous system, skeletal muscle and lung, as well as body temperature regulation. Skeletal muscle is a key determinant of basal metabolic rate and systemic energy metabolism. It contains Myopsin (SLN) which plays an important role in muscle heat production and energy metabolism. Melamine cyanuric acid (MCA) is an important component of the new flame retardant, but also a chemical interfering substance that can affect the endocrine in the body. It is mainly distributed in nylon and other flame retardant substances. Therefore, in this study, male mice were exposed to MCA at 10, 20 and 30 mg/kg for four weeks. We explored the effects of MCA exposure on skeletal muscle morphology, thermogenic gene expression and motor activity to explore whether MCA exposure could induce skeletal muscle hyperthermia and energy metabolism disorders and its underlying mechanisms. The results showed that the motor activity of male mice exposed to MCA was decreased, the morphology of skeletal muscle tissue was impaired, and the levels of morphological and thermogenic genes in skeletal muscle were destroyed. These findings are intended to provide a preliminary reference for studying the effects of MCA exposure on thermogenesis and energy metabolism in adult mice.
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Retardadores de Chama , Camundongos , Masculino , Animais , Retardadores de Chama/análise , Retardadores de Chama/metabolismo , Metabolismo Energético/fisiologia , Termogênese/fisiologia , Músculo Esquelético/metabolismo , Atividade MotoraRESUMO
Propionate is an effective mould inhibitor widely used as a food preservative. In this study, we used zebrafish to explore the adverse effects of long-term exposure to low concentrations of sodium propionate and the underlying molecular mechanisms (from larvae to adult). When exposed for 3 months, we found that blood glucose, total cholesterol, and triglyceride levels increased, and zebrafish developed a hyperglycaemic state. New tank test results showed depression in zebrafish reduced 5-hydroxytryptamine levels in the brain and damaged the dopamine system. At the same time, the results of the color preference test showed that zebrafish had cognitive impairments. In addition, Hypothalamic-Pituitary-Adrenal axis analysis revealed abnormal gene expression, increased cortisol levels, and reduced glucocorticoid receptor mRNA levels, which were consistent with depressive behavior. We also observed abnormal transcription of inflammatory and apoptotic factors. Overall, we found that chronic exposure to sodium propionate induces depressive symptoms. This may be related to the activation of the HPA axis by the hyperglycaemic state, thereby inducing inflammation and disrupting the dopaminergic system. In summary, this study provides theoretical and technical support for the overlap of the emotional pathogenesis associated with diabetes.
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Hiperglicemia , Doenças do Sistema Nervoso , Animais , Glicemia/metabolismo , Colesterol , Dopamina/metabolismo , Conservantes de Alimentos/metabolismo , Conservantes de Alimentos/farmacologia , Hidrocortisona/metabolismo , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Propionatos/metabolismo , Propionatos/toxicidade , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/metabolismo , Serotonina/metabolismo , Triglicerídeos/metabolismo , Triglicerídeos/farmacologia , Peixe-Zebra/metabolismoRESUMO
6-BA is a common plant growth regulator, but its safety has not been conclusive. The heart is one of the most important organs of living organisms, and the cardiogenesis process of zebrafish is similar to that of humans. Therefore, based on wild-type and transgenic zebrafish, we explored the development of zebrafish heart under 6-BA exposure and its mechanism. We found that 6-BA affected larval cardiogenesis, inducing defective expression of key genes for cardiac development (myl7, vmhc, and myh6) and AVC differentiation (bmp4, tbx2b, and notch1b), ultimately leading to weakened cardiac function (heart rate, diastolic speed, systolic speed). Acridine orange staining showed that the degree of apoptosis in zebrafish hearts was significantly increased under 6-BA, and the expression of cell-cycle-related genes was also changed. In addition, HPA axis assays revealed abnormally expressed mRNA levels of genes and significantly increased cortisol contents, which was also consistent with the observed anxiety behavior in zebrafish at 3 dpf. Transcriptional abnormalities of pro- and anti-inflammatory factors in immune signaling pathways were also detected in qPCR experiments. Collectively, we found that 6-BA induced cardiotoxicity in zebrafish, which may be related to altered HPA axis activity and the onset of inflammatory responses under 6-BA treatment.
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Cardiotoxicidade , Peixe-Zebra , Animais , Compostos de Benzil , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Embrião não Mamífero/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Purinas , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Decabromodiphenyl ethane (DBDPE) is a novel retardant. DBDPE is used in various flammable consumer products such as electronics, building materials, textiles, and children's toys. The presence of DBDPE in humans makes it extremely urgent to assess the health effects of DBDPE exposure. Here, we used female mice as an animal model to investigate the effects of DBDPE on embryonic development and offspring health. The results showed that 50 µg/kg bw/day of DBDPE exposure did not affect spindle rotation in oocytes after fertilization, but led to a decrease of pronuclei (PN) in zygotes. Further investigation found that DBDPE interferes with the self-assembly of F-actin in PN, resulting in PN reduction, DNA damage, and reduced expression of zygotic genome activating genes, and finally leading to abnormal embryonic development. More importantly, we found that maternal DBDPE exposure did not affect the growth and development of the first generation of offspring (F1) mice, but resulted in behavioral defects in F1 mice. Female F1 mice from DBDPE-exposed mothers exhibited increased motor activity and deficits in social behavior. Both female and male F1 mice from DBDPE-exposed mothers exhibited cognitive memory impairment. These results suggest that DBDPE has developmental toxicity on embryos and has a cross-generational interference effect. It is suggested that people should pay attention to the reproductive toxicity of DBDPE. In addition, it also provides a reference for studying the origin of neurological diseases and indicates that adult diseases caused by environmental pollutants may have begun in the embryonic stage.
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Retardadores de Chama , Actinas , Adulto , Animais , Bromobenzenos , Criança , Cognição , Desenvolvimento Embrionário , Feminino , Retardadores de Chama/toxicidade , Humanos , Masculino , Camundongos , ZigotoRESUMO
Sodium propionate is widely used as a preservative in food. The widespread use of preservatives is known to cause both environmental and public health problems. This study aimed to investigate the effects of sodium propionate on the developmental behavior and glucose metabolism of zebrafish. Our results showed that sodium propionate had no significant effect on the embryonic morphological development of zebrafish embryos but changed the head eye area. Then we found sodium propionate disturbed the thigmotaxis behavior, impaired neural development. Moreover, changes in clock gene expression disrupted the circadian rhythm of zebrafish. Circadian genes regulated insulin sensitivity and secretion in various tissues. Then our results showed that the disorder of circadian rhythm in zebrafish affected glucose metabolism and insulin resistance, which damaged the development of retina. Therefore, the safety of propionate should be further evaluated.
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Resistência à Insulina , Peixe-Zebra , Animais , Ritmo Circadiano , Glucose/metabolismo , Propionatos/toxicidade , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismoRESUMO
AIMS: Fluorene-9-bisphenol (BHPF), as a substitute for bisphenol A, is used in many industries in daily life. Many studies have clarified its effects as an endocrine disruptor on organisms, but its effect on lipid metabolism of zebrafish larvae is not clear. Patients with non-alcoholic fatty liver disease (NAFLD) are more susceptible to external pollutants. It is not clear how BHPF perturbs lipid metabolism or promotes NAFLD progression. MAIN METHODS: We explored the biological effects of BHPF on locomotor activity, inflammatory response, endoplasmic reticulum (ER) stress and lipid metabolism in zebrafish, especially in the mechanism of lipid homeostasis disorder. In addition, the role of BHPF in the progression of non-alcoholic fatty liver disease (NAFLD) was further explored. KEY FINDINGS: We found that high concentration (100 nmol/L) BHPF caused retarded growth, mild lipid accumulation and reduced the locomotive activity of zebrafish larvae, accompanied by a decrease in endogenous cortisol level. At the same time, it caused the full activation of inflammation and ER stress. Rescue experiments by 25(OH)D3 demonstrated that high concentration of BHPF caused defects in 1,25(OH)2D3 metabolic pathway through downregulation of cyp2r1, which further damaged pgc1a-mediated fatty acid oxidation and mitochondrial function, resulting in lipid accumulation. In summary, exposure to BHPF could damage lipid homeostasis and worsen the diet-induced NAFLD. SIGNIFICANCE: Our findings provide new insights into the role of BHPF in development of overweight and obesity and also improve understanding of its toxicological mechanism. Our results play a warning role in the administration of environmental pollutants.
Assuntos
Compostos Benzidrílicos/toxicidade , Ácidos Graxos/química , Fluorenos/toxicidade , Larva/efeitos dos fármacos , Transtornos do Metabolismo dos Lipídeos/patologia , Locomoção/efeitos dos fármacos , Fenóis/toxicidade , Animais , Larva/metabolismo , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/metabolismo , Peixe-ZebraRESUMO
Venlafaxine, a serotonin-noradrenaline reuptake inhibitor, is a widely used antidepressant drug routinely detected in aquatic environments. However, its potential impact on courtship behaviour in zebrafish is unknown. We tested the hypothesis that venlafaxine disrupts brain monoamine levels and molecular responses essential for courtship behaviour in zebrafish. Zebrafish (Danio rerio) were exposed to venlafaxine (1, 10, and 100 µg/L) for 20 days. We evaluated the molecular levels and neuronal basis of the effect of venlafaxine on courtship behaviour. Here, we show that venlafaxine inhibited courtship behaviour in zebrafish and increased the transcript levels of 5-ht1a and 5-ht2c while decreasing the transcript levels of genes involved in the dopaminergic system, including th1, th2, drd1b, and drd2b. Venlafaxine upregulated 5-HT levels and downregulated dopamine levels. Moreover, the subordinate fish from the venlafaxine-exposed group had significantly lower motor activity than the subordinate fish of the control group. Collectively, our results reveal that venlafaxine can disturb brain monoamine levels, affecting courtship behaviour in adult zebrafish.
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Poluentes Químicos da Água , Peixe-Zebra , Animais , Antidepressivos , Corte , Dopamina , Serotonina , Cloridrato de Venlafaxina/toxicidade , Poluentes Químicos da Água/toxicidadeRESUMO
The suprachiasmatic nucleus (SCN) is the main control area of the clock rhythm in the mammalian brain. It drives daily behaviours and rhythms by synchronizing or suppressing the oscillations of clock genes in peripheral tissue. It is an important brain tissue structure that affects rhythm stability. SCN has high plasticity and is easily affected by the external environment. In this experiment, we found that exposure to the endocrine disruptor 17ß-trenbolone (17ß-TBOH) affects the rhythmic function of SCN in the brains of adolescent male balb/c mice. Behavioural results showed that exposure to 17ß-TBOH disrupted daily activity-rest rhythms, reduced the robustness of endogenous rhythms, altered sleep-wake-related behaviours, and increased the stress to light stimulation. At the cellular level, exposure to 17ß-TBOH decreased the c-fos immune response of SCN neurons to the large phase shift, indicating that it affected the coupling ability of SCN neurons. At the molecular level, exposure to 17ß-TBOH interfered with the daily expression of hormones, changed the expression levels of the core clock genes and cell communication genes in the SCN, and affected the expression of wake-up genes in the hypothalamus. Finally, we observed the effect of exposure to 17ß-TBOH on energy metabolism. The results showed that 17ß-TBOH reduced the metabolic response and affected the metabolic function of the liver. This study revealed the influence of environmental endocrine disrupting chemicals (EDCs) on rhythms and metabolic disorders, and provides references for follow-up research.
Assuntos
Ritmo Circadiano , Disruptores Endócrinos , Animais , Encéfalo , Disruptores Endócrinos/toxicidade , Masculino , Camundongos , Núcleo Supraquiasmático , Acetato de TrembolonaRESUMO
Decabromodiphenyl ethane (DBDPE) is a novel flame retardant that is widely used in plastics, electronic products, building materials and textiles. Our previous studies have revealed the oocyte toxicity of DBDPE, but the effect of DBDPE on preimplantation embryo development has not been reported. Here, we investigated whether and how DBDPE exposure affects preimplantation embryo development. Adult female mice were orally exposed to DBDPE (0, 5, 50, 500 µg/kg bw/day) for 14 days. First, we found that after DBDPE exposure, mice showed obvious circadian rhythm disorder. Moreover, the development of preimplantation embryos was inhibited in DBDPE-exposed mice after pregnancy. Then, we further explored and revealed that DBDPE exposure reduced the endogenous melatonin (MLT) level during pregnancy, thereby inhibiting the development of preimplantation embryos. Furthermore, we discovered that exogenous MLT supplementation (15 mg/kg bw/day) rescued the inhibition of preimplantation embryo development induced by DBDPE, and a mechanistic study demonstrated that exogenous MLT inhibited the overexpression of ROS and DNA methylation at the 5-position of cytosine (5-mC) in DBDPE-exposed preimplantation embryos. Simultaneously, MLT ameliorated the DBDPE-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential (MMP), ATP, and Trp1 expression. Additionally, MLT restored DBDPE-induced changes in zona pellucida (ZP) hardness and trophectoderm (TE) cortical tension. Finally, the protective effect of MLT on embryos ameliorated the adverse reproductive outcomes (dead fetus, fetus with abnormal liver, fetal weight loss) induced by DBDPE. Collectively, DBDPE induced preimplantation embryo damage leading to adverse reproductive outcomes, and MLT has emerged as a potential tool to rescue adverse reproductive outcomes induced by DBDPE.
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Transtornos Cronobiológicos , Melatonina , Animais , Bromobenzenos , Ritmo Circadiano , Desenvolvimento Embrionário , Feminino , CamundongosRESUMO
MCA is a halogen-free flame retardant. It can cause damage to other tissues such as the kidneys and liver. However, the effects on the circadian rhythm and thyroid in adult mice have not been studied. In this article, adult male mice received MCA at concentrations of 0, 10, 20, 30 mg/kg. The results showed that the time spending on wheel-running and rest bouts changed in different period after MCA exposure. MCA disrupted the T3 and T4 hormone homeostasis and decreased the expression of thyroid hormone synthesis genes. The histological morphology of the thyroid gland was damaged. It was suggested that MCA exposure caused circadian rhythm disorder and thyroid dysfunction.