Epigenetic effects of insecticides on early differentiation of mouse embryonic stem cells

Wang, Wenlong; Ito, Tomohiro; Otsuka, Shuzo; Nansai, Hiroko; Abe, Kuniya; Nakao, Yoichi; Ohgane, Jun; Yoneda, Minoru; Sone, Hirohito

doi:10.1016/j.tiv.2021.105174

Cited by 9 publications

(8 citation statements)

References 47 publications

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“…IMI can alter early development in mammals (e.g., mice). These alterations were found to be related to C5-cytosine methylation due to exposure to this neonicotinoid pesticide [200]. Exposure to acetamiprid has been found to be linked to DNAm in rat brain and liver [201].…”

Section: Neonicotinoid Insecticidesmentioning

confidence: 93%

Insect Epigenetic Mechanisms Facing Anthropogenic-Derived Contamination, an Overview

Olivares-Castro

Cáceres-Jensen

Guerrero-Bosagna

et al. 2021

Insects

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Currently, the human species has been recognized as the primary species responsible for Earth’s biodiversity decline. Contamination by different chemical compounds, such as pesticides, is among the main causes of population decreases and species extinction. Insects are key for ecosystem maintenance; unfortunately, their populations are being drastically affected by human-derived disturbances. Pesticides, applied in agricultural and urban environments, are capable of polluting soil and water sources, reaching non-target organisms (native and introduced). Pesticides alter insect’s development, physiology, and inheritance. Recently, a link between pesticide effects on insects and their epigenetic molecular mechanisms (EMMs) has been demonstrated. EMMs are capable of regulating gene expression without modifying genetic sequences, resulting in the expression of different stress responses as well as compensatory mechanisms. In this work, we review the main anthropogenic contaminants capable of affecting insect biology and of triggering EMMs. EMMs are involved in the development of several diseases in native insects affected by pesticides (e.g., anomalous teratogenic reactions). Additionally, EMMs also may allow for the survival of some species (mainly pests) under contamination-derived habitats; this may lead to biodiversity decline and further biotic homogenization. We illustrate these patterns by reviewing the effect of neonicotinoid insecticides, insect EMMs, and their ecological consequences.

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Section: Neonicotinoid Insecticidesmentioning

confidence: 93%

Insect Epigenetic Mechanisms Facing Anthropogenic-Derived Contamination, an Overview

Olivares-Castro

Cáceres-Jensen

Guerrero-Bosagna

et al. 2021

Insects

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“…A previous study evaluated the effect of imidacloprid on the methylation status in the mouse embryonic stem cells in 1 × 10 −8 to 1 × 10 −6 M concentrations for 48 h, which showed an increase in the 5-mC% status, and decreased methylation of cell apoptosis, cell adhesion and tissue development genes such as Cdkn2 , Apc , Cdh1 , Timp3 and Rarb . 51 To the best of our knowledge, there are no studies evaluating the epigenetic effects of thiamethoxam in mammalian models or in the other ecosystem organisms. In the present study, exposure of SH-SY5Y cells to thiamethoxam for 24 hours elevated 5-mC% status; however, thiamethoxam induced non-significant changes in the expression of DNA methylation-related genes.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Global DNA Methylation in SH-SY5Y Cells Exposed to the Neonicotinoid Insecticides Imidacloprid and Thiamethoxam

et al. 2023

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Neonicotinoid insecticides, known for their selectivity and low mammalian toxicity, have been widely used in recent years as alternatives to organophosphate insecticides. Although neonicotinoids are generally considered to be safe, data show that they can cause harmful effects on human and environmental health. Due to the lack of information on their mechanism of toxicity, the effects of imidacloprid and thiamethoxam on DNA methylation as the most used marker for epigenetic effects were investigated in human neuroblastoma (SH-SY5Y) cells. The cells were exposed to imidacloprid and thiamethoxam in concentrations of 100, 200, and 500 μM for 24 hours, then global DNA methylation and expression of genes involved in global DNA methylation ( DNMT1, DNMT3a and DNMT3b) were investigated. Global DNA methylation significantly increased after imidacloprid exposure at 100 μM, and thiamethoxam exposures at 200 µM and 500 μM (>1.5-fold). Imidacloprid significantly decreased the expression of DNMT1 and DNMT3a, whereas thiamethoxam did not cause any significant changes in the expression of DNMT genes. Our findings suggested that alteration in global DNA methylation may be involved in the toxic mechanisms of imidacloprid and thiametoxam.

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“…Image acquisition and analysis were performed using IN Cell Analyzer 1000 (the current name Cytiva Tokyo, Japan was previously known as GE Healthcare UK Ltd.) as previously described 21 . Briefly, immunofluorescent images (nine fields per each well in a 96-well plate) were obtained using an automated IN Cell Analyzer 1000 (20× objective lens).…”

Section: Methodsmentioning

confidence: 99%

“…The MBD suppresses gene expression by binding to methylated promoter regions and, together with other histone modifications, induces changes in the chromatin structure 19 . Previous studies using mouse embryonic stem (ES) cells transfected with a fusion gene consisting of the MBD, enhanced green fluorescent protein, and nuclear localization signal (nls) showed that the localization of the MBD protein in the nuclei changed depending on exposure to insecticides or the differentiation status of cells 20 , 21 . Another report showed MBD associated with global DNA methylation in ES cells or differentiated cells during early development 22 .…”

Section: Introductionmentioning

confidence: 99%

iGEM as a human iPS cell-based global epigenetic modulation detection assay provides throughput characterization of chemicals affecting DNA methylation

Otsuka

Qin

Wang

et al. 2023

Sci Rep

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Chemical-induced dysregulation of DNA methylation during the fetal period is known to contribute to developmental disorders or increase the risk of certain diseases later in life. In this study, we developed an iGEM (iPS cell-based global epigenetic modulation) detection assay using human induced pluripotent stem (hiPS) cells that express a fluorescently labeled methyl-CpG-binding domain (MBD), which enables a high-throughput screening of epigenetic teratogens/mutagens. 135 chemicals with known cardiotoxicity and carcinogenicity were categorized according to the MBD signal intensity, which reflects the degree of nuclear spatial distribution/concentration of DNA methylation. Further biological characterization through machine-learning analysis that integrated genome-wide DNA methylation, gene expression profiling, and knowledge-based pathway analysis revealed that chemicals with hyperactive MBD signals strongly associated their effects on DNA methylation and expression of genes involved in cell cycle and development. These results demonstrated that our MBD-based integrated analytical system is a powerful framework for detecting epigenetic compounds and providing mechanism insights of pharmaceutical development for sustainable human health.

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Epigenetic effects of insecticides on early differentiation of mouse embryonic stem cells

Cited by 9 publications

References 47 publications

Insect Epigenetic Mechanisms Facing Anthropogenic-Derived Contamination, an Overview

Insect Epigenetic Mechanisms Facing Anthropogenic-Derived Contamination, an Overview

Assessment of Global DNA Methylation in SH-SY5Y Cells Exposed to the Neonicotinoid Insecticides Imidacloprid and Thiamethoxam

iGEM as a human iPS cell-based global epigenetic modulation detection assay provides throughput characterization of chemicals affecting DNA methylation

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