TY - JOUR
T1 - Epigenetic effects of insecticides on early differentiation of mouse embryonic stem cells
AU - Wang, Wenlong
AU - Ito, Tomohiro
AU - Otsuka, Satoshi
AU - Nansai, Hiroko
AU - Abe, Kuniya
AU - Nakao, Yoichi
AU - Ohgane, Jun
AU - Yoneda, Minoru
AU - Sone, Hideko
N1 - Funding Information:
This study was supported by a 15H01749 , Grant-in-Aid for Scientific Research (A) by Japan Society for the Promotion of Science .
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Developmental toxicity
KW - Mouse embryonic stem cells
KW - Pesticides
UR - http://www.scopus.com/inward/record.url?scp=85105834251&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85105834251&partnerID=8YFLogxK
U2 - 10.1016/j.tiv.2021.105174
DO - 10.1016/j.tiv.2021.105174
M3 - Article
C2 - 33865946
AN - SCOPUS:85105834251
SN - 0887-2333
VL - 75
JO - Toxicology in Vitro
JF - Toxicology in Vitro
M1 - 105174
ER -