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

Wenlong Wang, Tomohiro Ito, Satoshi Otsuka, Hiroko Nansai, Kuniya Abe, Yoichi Nakao, Jun Ohgane, Minoru Yoneda, Hideko Sone

Research output: Contribution to journalArticlepeer-review

Abstract

Increasing evidence indicates that many insecticides produce significant epigenetic changes during embryogenesis, leading to developmental toxicities. However, the effects of insecticides on DNA methylation status during early development have not been well studied. We developed a novel nuclear phenotypic approach using mouse embryonic stem cells harboring enhanced green fluorescent protein fused with methyl CpG-binding protein to evaluate global DNA methylation changes via high-content imaging analysis. Exposure to imidacloprid, carbaryl, and o,p'-DDT increased the fluorescent intensity of granules in the nuclei, indicating global DNA methylating effects. However, DNA methylation profiling in cell-cycle-related genes, such as Cdkn2a, Dapk1, Cdh1, Mlh1, Timp3, and Rarb, decreased in imidacloprid treatments, suggesting the potential influence of DNA methylation patterns on cell differentiation. We developed a rapid method for evaluating global DNA methylation and used this approach to show that insecticides pose risks of developmental toxicity through DNA methylation.

Original languageEnglish
Article number105174
JournalToxicology in Vitro
Volume75
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • Developmental toxicity
  • DNA methylation
  • Mouse embryonic stem cells
  • Pesticides

ASJC Scopus subject areas

  • Toxicology

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