Hematopoietic stem cell and immunotoxicity in zebrafish embryos induced by exposure to Metalaxyl-M

Zeng, Suwen; Peng, Yuyang; Ma, Jinze; Ge, Yurui; Huang, Yong; Xie, Shuling; Yuan, Wei; Chen, Lu; Zhang, Hua; Luo, Qiang; Liao, Xinjun; Lu, Huiqiang

doi:10.1016/j.scitotenv.2021.152102

Cited by 11 publications

(4 citation statements)

References 32 publications

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“…For example, exposure to cyhalofop-butyl (herbicide), bifenazate (acaricide) and metalaxyl-M (fungicide) significantly reduced the number of immune cells and led to immunotoxicity of zebrafish. [26][27][28] Metabolomics can study the relationship between metabolites and the physiopathology of the body. To clarify the underlying mechanism of EMB toxicity to zebrafish, the non-targeted metabolomics approach was used to profile the metabolic alterations of zebrafish.…”

Section: Discussionmentioning

confidence: 99%

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Studies on immunotoxicity induced by emamectin benzoate in zebrafish embryos based on metabolomics

Wei,

Wang,

et al. 2023

Environmental Toxicology

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Emamectin benzoate (EMB) is an insecticide for the control of agricultural lepidoptera pests, and also an anti‐parasiticide for the control of exoparasites in aquaculture industry. Increased studies suggest that EMB could cause toxicity to non‐targeted organisms, but its immunotoxicity to human remains unclear. In this study, zebrafish were used to investigate the immunotoxic effects induced by environmentally relevant doses of EMB. We observed that EMB exposure led to embryo mortality and delayed hatching, as well as increased malformations. Meanwhile, zebrafish exposed to EMB exhibited a significant decrease in the number of neutrophils and macrophages. In addition, untargeted metabolomics approach was developed to elucidate the mechanism of EMB‐induced immunotoxicity. We found that a total of 10 shared biomarkers were identified in response to EMB exposure. Furthermore, pathway analysis identified glycerophospholipid metabolism was the most relevant pathway. Within this pathway, it was observed abnormal increases in glycerol 3‐phosphate content, which could be attributed to the increased expression of GK5 and decreased expression of GPAT3. Our study provided novel and robust perspectives, which showed that EMB exposure to zebrafish embryos could cause metabolic disturbances that adversely affected development and immune system.

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Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that many pesticides can cause immunotoxicity by injuring to immune cells in zebrafish. For example, exposure to cyhalofop‐butyl (herbicide), bifenazate (acaricide) and metalaxyl‐M (fungicide) significantly reduced the number of immune cells and led to immunotoxicity of zebrafish 26–28 …”

Section: Discussionmentioning

confidence: 99%

Studies on immunotoxicity induced by emamectin benzoate in zebrafish embryos based on metabolomics

Wei,

Wang,

et al. 2023

Environmental Toxicology

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“…From these articles, immunotoxicity is mainly manifested in zebrafish embryos, larva liver, intestine, and adult ovary. Immunotoxicity test of zebrafish embryos with metalaxyl‐m (MM) (Zeng et al, 2022) and TCS (Zhao, Xie, et al, 2022), where MM could inhibit the development of hepatic stellate cells (HSCs) through activation of wingless/integrated (WNT) signaling pathway, reduce the number of immune cells, lead to inflammatory response, and affect the expression of immune‐related genes. This is the first experiment to evaluate the immunotoxicity of MM against zebrafish embryos.…”

Section: Reproductive Toxicity and Immunotoxicity In Zebrafishmentioning

confidence: 99%

Frontier of toxicology studies in zebrafish model

Shao,

Xiao,

Yang

et al. 2023

J of Applied Toxicology

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Based on the 87 original publications only from quartiles 1 and 2 of Journal Citation Report (JCR) collected by the major academic databases (Science Direct, Web of Science, PubMed, and Wiley) in 2022, the frontier of toxicology studies in zebrafish model is summarized. Herewith, a total of six aspects is covered such as developmental, neurological, cardiovascular, hepatic, reproductive, and immunizing toxicities. The tested samples involve chemicals, drugs, new environmental pollutants, nanomaterials, and its derivatives, along with those related mechanisms. This report may provide a frontier focus benefit to researchers engaging in a zebrafish model for environment, medicine, food, and other fields.

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“…Neutrophil deficiency (neutropenia), resulting from congenital conditions [10,11] or chemotherapeutic treatments [12,13], increase susceptibility to infections [14,15] and worsen the overall clinical picture of the patient. Notably, the exposure to different classes of environmentally relevant pollutants [16][17][18] has also been associated with neutropenia, urging the development of high-throughput assays to screen for chemicals that affect neutrophil counts. Zebrafish is now recognized as a mainstay vertebrate model to study innate immunity: the zebrafish hematopoietic program is highly conserved with higher vertebrates [19] and each spawn can yield hundreds of transparent embryos that, as early as 48 hours post fertilization (hpf), exhibit mature neutrophils [20].…”

Section: Introductionmentioning

confidence: 99%

Automated, high-throughput quantification of EGFP-expressing neutrophils in zebrafish by machine learning and a highly-parallelized microscope

Efromson,

Ferrero,

Bègue

et al. 2023

PLoS ONE

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Normal development of the immune system is essential for overall health and disease resistance. Bony fish, such as the zebrafish (Danio rerio), possess all the major immune cell lineages as mammals and can be employed to model human host response to immune challenge. Zebrafish neutrophils, for example, are present in the transparent larvae as early as 48 hours post fertilization and have been examined in numerous infection and immunotoxicology reports. One significant advantage of the zebrafish model is the ability to affordably generate high numbers of individual larvae that can be arrayed in multi-well plates for high throughput genetic and chemical exposure screens. However, traditional workflows for imaging individual larvae have been limited to low-throughput studies using traditional microscopes and manual analyses. Using a newly developed, parallelized microscope, the Multi-Camera Array Microscope (MCAM™), we have optimized a rapid, high-resolution algorithmic method to count fluorescently labeled cells in zebrafish larvae in vivo. Using transgenic zebrafish larvae, in which neutrophils express EGFP, we captured 18 gigapixels of images across a full 96-well plate, in 75 seconds, and processed the resulting datastream, counting individual fluorescent neutrophils in all individual larvae in 5 minutes. This automation is facilitated by a machine learning segmentation algorithm that defines the most in-focus view of each larva in each well after which pixel intensity thresholding and blob detection are employed to locate and count fluorescent cells. We validated this method by comparing algorithmic neutrophil counts to manual counts in larvae subjected to changes in neutrophil numbers, demonstrating the utility of this approach for high-throughput genetic and chemical screens where a change in neutrophil number is an endpoint metric. Using the MCAM™ we have been able to, within minutes, acquire both enough data to create an automated algorithm and execute a biological experiment with statistical significance. Finally, we present this open-source software package which allows the user to train and evaluate a custom machine learning segmentation model and use it to localize zebrafish and analyze cell counts within the segmented region of interest. This software can be modified as needed for studies involving other zebrafish cell lineages using different transgenic reporter lines and can also be adapted for studies using other amenable model species.

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Hematopoietic stem cell and immunotoxicity in zebrafish embryos induced by exposure to Metalaxyl-M

Cited by 11 publications

References 32 publications

Studies on immunotoxicity induced by emamectin benzoate in zebrafish embryos based on metabolomics

Studies on immunotoxicity induced by emamectin benzoate in zebrafish embryos based on metabolomics

Frontier of toxicology studies in zebrafish model

Automated, high-throughput quantification of EGFP-expressing neutrophils in zebrafish by machine learning and a highly-parallelized microscope

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