ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Zekun Li,Kun Jia,Xiaomei Chen,Jun Guo,Zhiguo Zheng,Weihua Chen,Yuan Peng,Yuhao Yang,Huiqiang Lu,Jian Yang
Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish ( Danio rerio ) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.
研究领域:
毒理学
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发育生物学
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水生毒理学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Xianhua Zhang,Runfa Wu,Fasheng Liu,Min Huang,Xiaoyan Huang,Nannan Wang,Qianqian Huang,Minhong Zhang,Xinjun Liao,Huiqiang Lu,Lan Liao
The combustion of biomass (e.g., wood, agricultural residues) and coal releases significant amounts of guaiacol (GUA) and its derivatives, major constituents of PM2.5 that threaten human health and ecosystems. GUA can rapidly enter the Earth's water circulation system through atmospheric deposition. However, its potential threat to aquatic organism and humans remains poorly understood. Using zebrafish—a model organism with high genetic homology to humans, transparent embryos, and rapid development—we investigated GUA’s ecological effects. Zebrafish embryos were exposed to 0.08–0.24 mM GUA from 12 to 120 h post-fertilization (hpf). GUA induced craniofacial malformations, behavioral abnormalities (reduced locomotion, impaired stimuli response), and oxidative stress via reactive oxygen species (ROS) accumulation. Disrupted migration, proliferation, and differentiation of cranial neural crest cells (NCCs) were observed, alongside altered Wnt signaling pathway gene expression. Both astaxanthin (AST, an ROS scavenger) and C59 (a Wnt inhibitor) could mitigate craniofacial defects. These findings demonstrate that GUA reduces antioxidant capacity, impairs NCCs function, and disrupts Wnt signaling, leading to craniofacial deformities. This study highlights GUA’s ecological and health risks, providing insights into its toxic mechanisms.
研究领域:
毒理学
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发育生物学
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环境科学
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分子生物学
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水生毒理学
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PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yiwen Zhou,Lili Chen,Miaomiao Han,Peixiang Zhu,Yanyi Wang,Xuanxuan Yu,Tingyu Reng,Huijuan Wang,Baochao Li,Caixia Zhang,Ziwei Huang,Shuang Lin,Guoyun Wang,Jie Ge,Baosheng Guo,Huang Li
Maxillary underdevelopment is a critical component of skeletal Class III malocclusion, closely linked to altered biomechanical signaling. Mechanical stimulation through early facemask protraction can effectively promote maxillary growth, yet the underlying mechanotransduction mechanisms remain unclear. In this study, fibroblast growth factor 9 (FGF9) is identified as a key biomechanical responder in maxillary development. Secreted predominantly by osteocytes, FGF9 interacts with fibroblast growth factor receptor 2 (FGFR2) on preosteoblasts to inhibit osteogenic differentiation. Mechanical stress reduces FGF9 secretion from osteocytes, thereby relieving its inhibitory effect and enhancing osteogenesis. Mechanistically, FGF9 promotes nuclear translocation of FGFR2 in preosteoblasts, which modulates transcription factors ATF5 and NR2F1 to suppress bone formation. In vivo, targeted overexpression of FGF9 in bone tissue led to significant maxillary growth impairment, underlying the pathological impact of disrupted mechanical signaling. These findings reveal a novel osteocyte–preosteoblast axis regulated by FGF9–FGFR2 signaling in response to mechanical stimulation and provide mechanistic insight into how biomechanical forces shape craniofacial development. This pathway offers new mechanistic insights and potential therapeutic targets for correcting craniofacial skeletal abnormalities.
研究领域:
发育生物学
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分子生物学
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生物力学
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颅面遗传学
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骨生物学
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转化医学
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PubMed
高影响因子
Cell Death & Disease
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2024
·Vol. 15
·期 3
·1-16
·
IF 8.1
Ma Lan,Zhou Xi,Yao Siyue,Zhang Xinyu,Mao Ji,Vona Barbara,Fan Liwen,Lou Shu,Li Dandan,Wang Lin,Pan Yongchu
Craniofacial malformations, often associated with syndromes, are prevalent birth defects. Emerging evidence underscores the importance of m 6 A modifications in various bioprocesses such as stem cell differentiation, tissue development, and tumorigenesis. Here, in vivo, experiments with zebrafish models revealed that mettl3 -knockdown embryos at 144 h postfertilization exhibited aberrant craniofacial features, including altered mouth opening, jaw dimensions, ethmoid plate, tooth formation and hypoactive behavior. Similarly, low METTL3 expression inhibited the proliferation and migration of BMSCs, HEPM cells, and DPSCs. Loss of METTL3 led to reduced mRNA m 6 A methylation and PSEN1 expression, impacting craniofacial phenotypes. Co-injection of mettl3 or psen1 mRNA rescued the level of Sox10 fusion protein, promoted voluntary movement, and mitigated abnormal craniofacial phenotypes induced by mettl3 knockdown in zebrafish. Mechanistically, YTHDF1 enhanced the mRNA stability of m 6 A-modified PSEN1 , while decreased METTL3-mediated m 6 A methylation hindered β-catenin binding to PSEN1, suppressing Wnt/β-catenin signaling. Pharmacological activation of the Wnt/β-catenin pathway partially alleviated the phenotypes of mettl3 morphant and reversed the decreases in cell proliferation and migration induced by METTL3 silencing. This study elucidates the pivotal role of METTL3 in craniofacial development via the METTL3/YTHDF1/PSEN1/β-catenin signaling axis.
研究领域:
发育生物学
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分子生物学
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遗传学
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细胞生物学
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高影响因子
International Journal of Oral Science
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2019
·Vol. 11
·期 1
·1-12
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IF 2.75
Jiang Yuanjing,Zhang Shixian,Mao Chuanqing,Lai Yongzhen,Wu Di,Zhao Hu,Liao Caiyu,Chen Weihui
The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg − 1 or 150 mg•kg − 1 body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg − 1 . Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
研究领域:
发育生物学
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分子生物学
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颅面发育
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PubMed
高影响因子
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