Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8552719 | Toxicology | 2018 | 10 Pages |
Abstract
Anti-thyroid drugs (ATDs) therapy is necessary for pregnant women with hyperthyroidism. However, there is a lack of studies on developmental toxicity of ATDs. In this study, we observed the developmental toxicity of fetal liver induced by prenatal methimazole exposure (PME) in mice, and explored the potential mechanism. Pregnant Kunming mice were administered intragastrically with 4.5 or 18â¯mg/kg·d methimazole from gestational day (GD) 9â¼18. After PME, the birth weights of the offspring mice were decreased, and the liver morphology, development indexes and metabolic function were all altered in different degree in the PME fetuses. Meanwhile, PME decreased the levels of serum and hepatic insulin-like growth factor 1 (IGF1), and reduced the gene expression of IGF1 downstream signaling pathway. Furthermore, the protein levels of phosphorylated-extracellular regulated protein kinases (p-ERK) and serine-threonine protein kinase (p-Akt) were also reduced. Furthermore, methimazole disturb hepatocyte differentiation, maturation and metabolic function through suppressing IGF1 signaling pathway in HepG2 cells. These results demonstrated that PME could induce fetal liver developmental toxicity, and the underlying mechanism was related to low-expression of hepatic IGF1 caused by methimazole, which mediated abnormal liver morphology and metabolic function.
Keywords
p-ERKPCNAPEPCKIGF-1RAKT2IUGRHMGCRERKGAPDHALBHNF4αPhosphorylated ERKHMG CoA reductaseIgf1p-AktAlbuminalpha fetoproteinProliferating Cell Nuclear AntigenAktfatty acid synthaseAFPgestational dayserine-threonine protein kinasePMEhepatocyte nuclear factor 4αintrauterine growth retardationinsulin-like growth factor 1Fasnphosphorylated Aktphosphoenolpyruvate carboxykinaseExtracellular regulated protein kinaseGlyceraldehyde phosphate dehydrogenaseInsulin-like growth factor-1 receptor
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Authors
Guihua Wang, Bo He, Wen Hu, Kexin Liu, Xiaohan Gong, Hao Kou, Yu Guo, Hui Wang,