PMID- 29990518
OWN - NLM
STAT- MEDLINE
DCOM- 20190411
LR  - 20190411
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 408
DP  - 2018 Sep 1
TI  - Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity 
      in fetal mice.
PG  - 70-79
LID - S0300-483X(18)30135-5 [pii]
LID - 10.1016/j.tox.2018.07.004 [doi]
AB  - 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 18 mg/kg.d methimazole from gestational day (GD) 9 approximately 18. 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.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Wang, Guihua
AU  - Wang G
AD  - Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan, 
      430071, China.
FAU - He, Bo
AU  - He B
AD  - Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan, 
      430071, China.
FAU - Hu, Wen
AU  - Hu W
AD  - Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan, 
      430071, China.
FAU - Liu, Kexin
AU  - Liu K
AD  - Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan, 
      430071, China.
FAU - Gong, Xiaohan
AU  - Gong X
AD  - Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan, 
      430071, China.
FAU - Kou, Hao
AU  - Kou H
AD  - Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan, 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan, 430071, China.
FAU - Guo, Yu
AU  - Guo Y
AD  - Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan, 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan, 430071, China. Electronic address: guoy@whu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan, 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan, 430071, China. Electronic address: wanghui19@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180707
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Antithyroid Agents)
RN  - 0 (IGF1 protein, human)
RN  - 0 (insulin-like growth factor-1, mouse)
RN  - 554Z48XN5E (Methimazole)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Antithyroid Agents/*toxicity
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Gestational Age
MH  - Hep G2 Cells
MH  - Hepatocytes/drug effects/metabolism/pathology
MH  - Humans
MH  - Insulin-Like Growth Factor I/genetics/*metabolism
MH  - Liver/*drug effects/embryology/metabolism
MH  - Maternal Exposure
MH  - Methimazole/*toxicity
MH  - Mice
MH  - Phosphorylation
MH  - Pregnancy
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Fetal liver developmental toxicity
OT  - Glucose and lipid metabolic function
OT  - Insulin-like growth factor 1 (IGF1)
OT  - Prenatal methimazole exposure
EDAT- 2018/07/11 06:00
MHDA- 2019/04/12 06:00
CRDT- 2018/07/11 06:00
PHST- 2018/02/05 00:00 [received]
PHST- 2018/06/03 00:00 [revised]
PHST- 2018/07/05 00:00 [accepted]
PHST- 2018/07/11 06:00 [pubmed]
PHST- 2019/04/12 06:00 [medline]
PHST- 2018/07/11 06:00 [entrez]
AID - S0300-483X(18)30135-5 [pii]
AID - 10.1016/j.tox.2018.07.004 [doi]
PST - ppublish
SO  - Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 
      7.