Triazole fungicides disrupt embryonic stem cell differentiation: Potential modulatory role of the retinoic acid signaling pathway.
Ecotoxicol Environ Saf
; 283: 116859, 2024 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-39137466
ABSTRACT
The developmental toxicity and human health risks of triazole fungicides (TFs) have attracted worldwide attention due to the ability to enter the human body in a variety of ways. Nevertheless, the specific mechanism by which TFs exert remains incompletely understood. Given that retinoic acid (RA) signaling pathway are closely related to development, this study aimed to screen and identify developmentally disabled chemicals in commonly used TFs and to reveal the potential effects of TFs on developmental retardation through the RA signaling pathway in mouse embryonic stem cells (mESCs). Specifically, six typical TFs (myclobutanil, tebuconazole, hexaconazole, propiconazole, difenoconazole, and flusilazole) were exposed through the construction of an embryoid bodies (EBs)-based in vitro global differentiation models. Our results clarified that various TFs disturbed lineage commitment during early embryonic development. Crucially, the activation of RA signaling pathway, which alters the expression of key genes and interferes the transport and metabolism of retinol, may be responsible for this effect. Furthermore, molecular docking, molecular dynamics simulations, and experiments using a retinoic acid receptor α inhibitor provide evidence supporting the potential modulatory role of the retinoic acid signaling pathway in developmental injury. The current study offers new insights into the TFs involved in the RA signaling pathway that interfere with the differentiation process of mESCs, which is crucial for understanding the impact of TFs on pregnancy and early development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tretinoína
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Triazóis
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Transdução de Sinais
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Diferenciação Celular
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Fungicidas Industriais
Limite:
Animals
Idioma:
En
Revista:
Ecotoxicol Environ Saf
/
Ecotoxicol. environ. saf
/
Ecotoxicology and environmental safety
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China