JOURNAL OF FISH BIOLOGY
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2016
·Vol. 88
·期 5
·1693-1707
·
IF 1.246
W. T. Zhang,K. Liu,J. S. Xiang,L. Y. Zhang,W. J. Liu,Z. D. Dong,Y. Z. Li,H. L. Li,S. L. Chen,N. Wang
To elucidate the effect of thyroid hormone receptor α A ( thraa ) on metamorphosis, the full length cDNA of half-smooth tongue sole Cynoglossus semilaevis was cloned. The relative gene transcript level of thraa at different development stages was quantified using real-time PCR. Transcription of thraa increased and declined rapidly during metamorphosis. Hyperthyroidism was induced in juveniles and larvae with exposure to T3 and T4, and hypothyroidism with thiourea (TU), 2-mercapto-1-methylimidazole (MMI). thraa mRNA was higher in fish treated for 6 days with MMI than in untreated controls, although inhibited larvae did not complete metamorphosis. The addition of exogenous T4 reversed this effect in the MMI-treated group, but not in the TU-treated group. In situ hybridization revealed progressive tail end of body growth and change during developmental stages, with corresponding changes in thraa expression. This process may be induced by thyroid hormones with thraa as a major mediator. The morphological changes of tip of the tail may be associated with the development of lateral swimming.
研究领域:
分子生物学
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内分泌学
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发育生物学
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水产养殖
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Chao Hu,Yeqing Xu,Mingmin Wang,Shixuan Cui,Hangjun Zhang,Liping Lu
Bisphenol analogues are widely used in industrial and daily-use consumer products having imperfect thyroid hormones (THs) structures. Widespread exposure interferes with thyroid-related health outcomes in human. The mechanisms of disruption on TH synthesis and subsequent thyroid dysfunction by different bisphenol analogues remain unclear. Here, we evaluated bisphenol-induced thyroid endocrine disruption in C57BL/6 mice at doses of 0.002, 0.02, 2, and 20 mg/kg body weight/day (BW/d) for five consecutive weeks. Administration of 20 mg/kg BW/d bisphenol S (BPS) and 2 mg/kg BW/d tetrabromobisphenol S (TBBPS) significantly increased serum thyrotropin (TSH) levels to 1.21-fold and 1.20-fold of control group, respectively, indicating that bisphenols induced thyroid dysfunction in mice. Height of the thyroid follicle epithelium significantly increased to 1.27-, 1.24-, 1.26-, and 1.36-fold compared to control group with BPA, BPS, TBBPA, and TBBPS at 20 mg/kg BW/d, respectively, indicating impairment of the thyroid gland structure, and TBBPS showed potent effect. Exposure to bisphenol analogues of 0.02 mg/kg BW/d downregulated the protein expression levels of thyrotropin receptor, the sodium/iodide symporter, thyroperoxidase. The TH-dependent effects were further determined using the T-Screen assay at 10 −11 M to 10 −5 M concentrations. Bisphenol analogues significantly decreased TH-dependent GH3 cell proliferation, indicating the antagonistic activity of bisphenol analogues. The gene responsible for THs synthesis of thyrotropin releasing hormone receptor and TSH were upregulated, but downregulation of thyroid receptor β was observed. Our results suggest that bisphenol analogues distinctly induce thyroid dysfunction via TH synthesis, implying adverse effect of bisphenol analogues on TH homeostasis and subsequent physiological processes.
研究领域:
内分泌学
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毒理学
·
环境健康
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2025
·
IF 7.3
Ping Ding,Jiayi Zhang,Xin Li,Pengcheng Ma,Guocheng Hu,Lijuan Zhang,Yunjiang Yu
The use of triclosan (TCS)-containing disinfectants has become increasingly prevalent in response to the COVID-19 pandemic, leading to a heightened presence of TCS in aquatic ecosystems. Thyroid hormones (THs), which are essential for numerous developmental and metabolic processes, are structurally similar to TCS, rendering it prone to exert endocrine-disrupting effects. In this study, we demonstrate that TCS can induce thyroid hormone disruption in zebrafish, with transgenerational consequences. Zebrafish embryos were exposed to environmentally relevant concentrations of TCS (0, 1, 3, and 10 μg/L) for 30, 60, and 180 days. TCS accumulated in zebrafish over an extended period, causing significant, dose-dependent alterations in TH levels. Furthermore, TCS significantly thereby interfered with the expression of thyroid axis-related genes in the P0-F1 generations. Molecular docking further confirmed that TCS induces transgenerational thyroid effects through potentially strong interactions with thyroglobulin (TG), interfering with the normal physiological function of THs. These findings suggest that TCS at environmentally relevant concentrations can exert ecologically harmful effects by disrupting THs. A rigorous ecological assessment of TCS is recommended before promoting or substituting antimicrobial agents in future disinfection products.
研究领域:
环境科学
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毒理学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2018
·
IF 4.244
Yuqing Zhang,Gongwei Sun,Yi Zhang,Biao Huang,Zhi Xing,Sichun Zhang,Xinrong Zhang
Inductively Coupled Plasma Mass Spectrometry (ICP-MS) based immunoassay method has been proposed in multiple immunoassays but has not been used in competitive and sandwich formats immunoassay simultaneously. The two immunoassays were usually conducted separately in clinical field depending on the size and the amount of binding sites of targets. We proposed an immunoassay method based on magnetic beads and ICP-MS detection that could be suitable for both small and large molecules. The functionalized magnetic beads were added to capture the immune complex after immune reaction. In this way, thyrotropin and free thyroid hormone can be captured, separated and then detected according to the elemental tags by ICP-MS simultaneously. The new method was evaluated by comparing the results with time resolved fluorescence immunoassays (TRFIA). The dynamic ranges of TSH and FT 4 were 0.16–105 mU/L and 3.5–65 pmol/L, respectively. The limits of detections were 0.06 mU/L for TSH and 1.59 pmol/L for FT 4 . And the relative standard deviations (RSD) of TSH and FT 4 were 4.64% at 2.5 mU/L and 1.87% at 5.85 pmol/L. This immunoassay method enables the determination of small and large biomolecules simultaneously via competitive and sandwich immunoassay formats.
研究领域:
分析化学
·
临床化学
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生物医学工程
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Junguo Ma,Chunyu Diao,Yidan Zhang,Huan Kang,Yiyi Feng,Yuanyuan Li,Xiaoyu Li
Fenpropathrin (FEN), a highly efficient and broad-spectrum synthetic pyrethroid insecticide. Although sufficient concern has been given to the negative impacts of FEN on non-target organisms, limited knowledge exists regarding the developmental effects of FEN. In this study, effects of FEN (0.45, 1.35, 4.05, and 12.15 μg/L) on various early life-stage endpoints of zebrafish were investigated from 3 to 144 h post-fertilization (hpf) in order to disclose the developmental effects and underlying mechanisms caused by FEN. The results indicate that exposure to FEN induced developmental toxicity in zebrafish, including decreased heart rate, reduced blood flow, shorter body length, smaller eye size, non-inflated swim bladder, and disrupted craniofacial chondrogenesis, which were possibly due to a significant decrease in the levels of thyroxine (T4), triiodothyronine (T3), insulin-like growth factor-1 (IGF-1), and growth hormone (GH), increase in lipid accumulation, and alteration in the contents of total cholesterol (T-CHO) and triglyceride (TG) in larvae exposed to FEN. Besides, FEN exposure also resulted in the inhibition of spontaneous movement of embryo at 24 hpf, a decline in touch evoke response (TER) at 72 hpf, and a reduction in free-swimming activity at 144 hpf, as well as the larval activity at 144 hpf during the dark-light transition stimulus. Mechanistic examinations have shown that FEN treatment inhibits the activities of AChE and elevates the ACh levels. In addition, FEN exposure increased ROS levels and altered the levels of malondialdehyde (MDA), and induced apoptosis as determined by acridine orange staining and elevated caspase-3 levels, suggesting that the involvement of oxidative stress and apoptosis in FEN-induced developmental toxicity of embryos. Transcriptome sequencing of larvae showed that FEN altered the expressions of multiple metabolic and nervous system pathways, including PPAR signaling pathway, lipid metabolism pathway, carbohydrate metabolism pathway, retinol metabolism pathway, and neuroactive ligand-receptor interaction pathway, demonstrating that FEN alters the normal development of zebrafish embryos, and multiple pathways mediating the FEN-induced developmental toxicity. Overall, these findings enhance our understanding of the developmental toxic effects of FEN and provide fundamental data for assessing the risk of FEN on non-target organisms.
研究领域:
环境科学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 3
·798
·
IF 4.927
Jinbo Li,Yuanyuan Li,Min Zhu,Shilin Song,Zhanfen Qin
There is a need for rapidly screening thyroid hormone (TH) signaling disruptors in vivo considering the essential role of TH signaling in vertebrates. We aimed to establish a rapid in vivo screening assay usingXenopus laevisbased on the T3-inducedXenopusmetamorphosis assay we established previously, as well as theXenopusEleutheroembryonic Thyroid Assay (XETA). Stage 48 tadpoles were treated with a series of concentrations of T3 in 6-well plates for 24 h and the expression of six TH-response genes was analyzed for choosing a proper T3 concentration. Next, bisphenol A (BPA) and tetrabromobisphenol A (TBBPA), two known TH signaling disruptors, were tested for determining the most sensitive TH-response gene, followed by the detection of several suspected TH signaling disruptors. We determined 1 nM as the induction concentration of T3 andthibzexpression as the sensitive endpoint for detecting TH signaling disruptors given its highest response to T3, BPA, and TBBPA. And we identified betamipron as a TH signaling agonist, and 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) as a TH signaling antagonist. Overall, we developed a multiwell-based assay for rapidly screening TH signaling disruptors usingthibzexpression as a sensitive endpoint inX. laevis.Keywords:thyroid hormone;screening assay;Xenopus laevis;thibzgene;multiwell plate
研究领域:
内分泌学
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毒理学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
BIOPHYSICAL CHEMISTRY
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2025
·
IF 2.2
Yanhong Zheng,Zeyu Song,Muwei Huang,Cancan Li,Chunke Nong,Tinghao Jiang,Zhanji Li,Zhongsheng Yi
Thyroxine (T4), as a type of thyroid hormone (TH), is a key hormone in regulating human metabolism, growth and development, central nervous system functions, and energy balance. It relies on TH transport proteins to reach cells and exert its biological actions. However, the binding of nitrophenol pollutants to TH transport proteins prevents the delivery of thyroid hormones to cells, thereby inhibiting the effects of the hormones. This study combines spectroscopic experiments and computational simulations to explore the mechanism of nitrophenols' interference with TH transport proteins. Detailed information on the quenching mechanism, binding parameters, interaction forces, binding models, and conformational changes of nitrophenols (PNP), chlorinated nitrophenols (CNP), and brominated nitrophenols (BNP) with TH transport proteins is obtained through spectroscopic experiments. Nitrophenols are found to form hydrogen bonds with residues Lys15, Arg378, and Arg381, respectively, thereby displacing T4 at the binding site in the TH transport proteins. With an increasing number of halogen atoms, the affinity of halogenated nitrophenols for TH transport proteins intensifies. Computational simulations are used to further understand the binding modes and binding sites, providing molecular-level insights into the binding of NPs in the cavity of TH transport proteins. Theoretical evidence from molecular docking and molecular dynamics (MD) simulations supports the experimental findings.
研究领域:
生物化学
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环境毒理学
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计算生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY
·
2018
·Vol. 27
·期 3
·313-324
·
IF 1.987
Dong Huike,Lu Guanghua,Yan Zhenhua,Liu Jianchao,Yang Haohan,Nkoom Matthew
As a cycloaliphatic brominated flame retardant, hexabromocyclododecane (HBCD) has been widely used in building thermal insulation and fireproof materials. However, there is little information on the bioconcentration as well as effects with respect to HBCD exposure in the aquatic environment. To investigate the bioconcentration of HBCD in tissues (muscle and liver) and its biochemical and behavioural effects, juvenile crucian carp ( Carassius auratus ) were exposed to different concentrations of technical HBCD (nominal concentrations, 2, 20, 200 μg/L) for 7 days, using a flow-through exposure system. HBCD was found to concentrate in the liver and muscle with a terminal concentration of 0.60 ± 0.22 μg/g lw (lipid weight) and 0.18 ± 0.02 μg/g lw, respectively, at an environmentally-relevant concentration (2 μg/L). The total thyroxine and total triiodothyronine in the fish plasma were lowered as a result of exposure to the HBCD. Acetylcholinesterase activity in the brain was increased, while swimming activity was inhibited and shoaling inclination was enhanced after exposure to 200 μg/L HBCD. Feeding rate was suppressed in the 20 and 200 μg/L treatment groups. In summary, HBCD concentrations 10–100× higher than the current environmentally-relevant exposures induced adverse effects in the fish species tested in this study. These results suggest that increasing environmental concentrations and/or species with higher sensitivity than carp might be adversely affected by HBCD.
研究领域:
环境科学
·
毒理学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Yide He,Xiang Li,Yan Yang,Rosa Freitas,Jiansheng Zhu,Guixiang Ji,Yongjun Zhang
Gabapentin (GBP), a pharmaceutical widely used for seizures and neuropathic pain, has emerged as a contaminant in global aquatic environments, raising concerns about its ecological impact. This study investigated the effects of environmentally relevant concentrations of GBP (0, 1, 10, 1000 μg/L) on visual development in zebrafish ( Danio rerio ). Behavioral assays showed that GBP exposure enhanced light sensitivity, as indicated by a significant increase in total travel distance (TTD) in all exposure groups compared to controls. The 1 μg/L and 1000 μg/L exposure groups demonstrated a 41 % and 37 % increase in TTD, respectively ( p < 0.05). Apoptosis assays revealed dose-dependent retinal cell death, with fluorescence intensity rising by 15 % at 1000 μg/L ( p < 0.05). Visual acuity, measured through optokinetic response (OKR) tests, decreased significantly across all color stimuli. Angular velocity under white light decreased from 4.0 °/s in controls to 1.6 °/s at 1000 μg/L ( p < 0.01) in a dose-de p endent manner. Retinal histopathology showed a 17 % increase in ganglion cell layer thickness at 1000 μg/L ( p < 0.05) in a dose-dependent manner. Thyroid hormone assays indicated significant reductions in T3 and T4 levels ( p < 0.001), with a 22 % increase in the T3/T4 ratio at 1000 μg/L. Gene expression analysis revealed dysregulation in apoptosis ( casp3a , ifi27 ), thyroid ( tshr , dio1 ), and retinal development ( atoh7 , pax6a ) pathways. These findings demonstrate that GBP disrupts visual development in zebrafish through retinal apoptosis and thyroid hormone dysregulation, highlighting the ecological risks posed by pharmaceutical pollutants. GBP exposure increased light-driven locomotor activity, indicating heightened light sensitivity due to apoptosis in the retina. Visual acuity was assessed through the optokinetic response (OKR) test, retinal morphology, and thyroid hormone (TH) levels. Even at concentrations as low as 1 µg/L, GBP exposure led to significant reductions in OKR across various colors, likely due to changes in retinal thickness linked to thyroid hormone disruption. These effects were consistent with alterations in gene expression related to apoptosis, the thyroid system, and retinal development. Our findings enhance understanding of how GBP exposure impairs vision in fish and highlight the need to evaluate the ecological risks of pharmaceutical contaminants in aquatic environments.
研究领域:
生态毒理学
·
神经生物学
·
内分泌干扰研究
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Fei Wei,Xueyi Wu,Hongyuan Wang,Yongpu Zhang,Lei Xie
Methimazole (MMI) is an emerging endocrine disrupting chemical (EDC) due to its increasing use in the treatment of thyrotoxicosis (hyperthyroidism), but its potential impact on amphibian development remains largely unexplored. In the present study, the effects of 8 mg/L MMI and 1 μg/L thyroxine (T4) exposure on skeletal ossification and muscle development in Bufo gargarizans tadpoles were comprehensively investigated by double skeletal staining, histological analysis and RNA sequencing. Our results indicated that MMI treatment down-regulated the expression levels of ossification-related genes (e.g., BMPs , MMPs , and Wnt9a ) in cartilage, thereby delaying chondrocyte apoptosis and inhibiting hindlimb ossification. Muscle sarcomere was elongated in both the MMI and T4 treatment groups, which may lead to muscle weakness and consequently affect land motion. Additionally, we evaluated the expression levels of fast muscle-related genes ( TNNI2 and TNNT3 ) and slow muscle-related genes ( TNNI1 and TNNT1 ), revealing an opposite trend in the transition from fast to slow muscle after T4 and MMI exposures. In conclusion, these findings fill the data gap regarding MMI contamination in aquatic environments by revealing the negative effects of MMI on amphibian bone and muscle development. Future studies should address the toxicity of EDCs to wildlife and inform aquatic ecosystem conservation strategies.
研究领域:
生态毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2019
·
IF 5.714
Fang Jiao,Kun Qiao,Yao Jiang,Shuying Li,Jinghao Zhao,Wenjun Gui
As a widely used organotin acaricide nowadays, azocyclotin (ACT) could induce thyroidal endocrine disruption in fishes and amphibians, but its dominant disrupting mode remains unknown. In this study, zebrafish were firstly exposed to ACT (0.18–0.36 ng/mL) from 2 hpf (hours post fertilization) to 30 dpf (days post fertilization), and a series of developmental toxicological endpoints and thyroid hormones were measured. Result showed that no developmental toxicity to zebrafish was found in 0.18 and 0.24 ng/mL groups except decreased body weight (30 dpf, 0.24 ng/mL). However, exposed to 0.36 ng/mL ACT led to reductions in heartbeat (48 hpf), hatching rate (72 hpf) and bodyweight (30 dpf). General tendencies of decreases in free T3 but increases in free T4 and reductions in ratio of free T3/T4 were also found, inferring that type II deiodinase (Dio2) was repressed. This inference was confirmed by Western analysis that Dio2 expression reduced by 42.7% after 0.36 ng/mL ACT treatment. Moreover, RNA-Seq analysis implied that exposed to 0.36 ng/mL ACT altered the genome-wide gene expression profiles of zebrafish. Totally 5660 genes (involving 3154 down-regulated and 2596 up-regulated genes) were differentially expressed, and 13 deferentially expressed genes including down-regulated dio2 were significantly enriched in thyroid hormone signaling pathway. Subsequently, an in vitro thyroid receptor-reporter gene assay using GH3 cells was performed to further explore the potential disrupting mechanism. Result showed that luciferase activity slightly increased after exposure to ACT alone or ACT combined with low level T3, but was suppressed when combined with high level T3. It indicted there probably existed a competitive relationship in some extent between ACT and T3 in vivo . Overall, the present study provided preliminary evidences that long-term exposure to trace ACT repressed Dio2 expression, declined T3 and then activated thyroid receptor-mediated signaling, thereby leading to integrated thyroid endocrine disruption in zebrafish larvae.
研究领域:
环境科学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Wenjuan Zhang,Aijing Li,Yu Pan,Fengbang Wang,Ming Li,Yong Liang,Xinglei Yao,Jinghai Song,Maoyong Song,Guibin Jiang
Tetrabromobisphenol A (TBBPA) is a widely used flame retardant , but the adverse outcomes induced by TBBPA has not been fully elucidated. In this study, TBBPA was detected in 54.9% of 102 female Chinese volunteers with an average serum concentration of 0.34 ng/mL. To investigate whether TBBPA induces adverse outcomes at environmentally relevant exposure doses, the mice were exposed to TBBPA for 14 and 28 days. The internal doses of TBBPA in mice serum were nearly the internal doses in volunteers. TBBPA significantly increased the secretion of some pro-inflammatory cytokines and suppressed immune responses in mice under such serum concentrations after 14- and 28-days exposure. Interestingly, uterine edema was observed in TBBPA-treated mice. In primary uterine cells model, the results showed TBBPA exposure suppressed THRβ expression, leading to the activation of the inflammatory PI3K/NF-κB signaling pathway. Our findings indicated that the uterus is the susceptible target organ of TBBPA and TBBPA exposure might increase risk of uterine cancer through deregulating inflammation pathways.
研究领域:
环境科学
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毒理学
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生殖健康
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）