PMID- 31811911
OWN - NLM
STAT- MEDLINE
DCOM- 20200127
LR  - 20200127
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 321
DP  - 2020 Mar 15
TI  - Prenatal ethanol exposure increased the susceptibility of adult offspring rats to 
      glomerulosclerosis.
PG  - 44-53
LID - S0378-4274(19)30383-2 [pii]
LID - 10.1016/j.toxlet.2019.11.026 [doi]
AB  - This study was aimed to investigate the effect of prenatal ethanol exposure (PEE) 
      on the susceptibility of offspring rats to glomerulosclerosis and to explore the 
      mechanism. Pregnant Wistar rats were intragastrically administered ethanol 
      (4g/kg.d) from gestational day (GD) 9 to GD 20, and the control group was given 
      equal volume of normal saline. The offspring rats were all fed with high-fat diet 
      after weaning, and were sacrificed at postnatal week 24 (PW24). The results 
      revealed that the adult offspring kidneys in the male and female PEE groups 
      exhibited higher glomerulosclerosis index and interstitial fibrosis index 
      compared with the high-fat diet control groups, accompanied by elevated serum 
      creatinine level. The protein expression of Nephrin and WT1, which were the 
      marker genes of podocytes, was significantly decreased, whereas the protein 
      expression of desmin and alpha-SMA, the marker genes of mesenchymal cells, was 
      remarked enhanced in the male and female PEE groups. Compared with the high-fat 
      diet control groups, the mRNA and protein expressions of renal angiotensin II 
      receptor type 2 (AT2R) were decreased in the male PEE group, but increased in the 
      female PEE group. PEE increased the mRNA and protein expressions of 
      glucocorticoid (GC) activation system and inhibited the expression of 
      insulin-like growth factor 1 (IGF1) signaling pathway in male offspring kidney; 
      on the contrary, in female offspring kidney, PEE inhibited the mRNA and protein 
      expression of glucocorticoid activation system and increased the expression of 
      IGF1 signaling pathway. Taken together, PEE increased the susceptibility of the 
      adult offspring to glomerulosclerosis, and the programming of renal AT2R or 
      GC-IGF1 is respectively involved in the toxicity of PEE to the male or female 
      offspring.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Chen, Haiyun
AU  - Chen H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Zhu, Yanan
AU  - Zhu Y
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Zhao, Xiaoqi
AU  - Zhao X
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - He, Hangyuan
AU  - He H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Luo, Jinsong
AU  - Luo J
AD  - Department of Paediatrics, People's Hospital of Wuhan University, Wuhan, 430060, 
      China.
FAU - Ao, Ying
AU  - Ao Y
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disorder, Wuhan, 430071, China. Electronic address: yingao@whu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disorder, Wuhan, 430071, China.
LA  - eng
PT  - Journal Article
DEP - 20191204
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Agtr2 protein, rat)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (insulin-like growth factor-1, rat)
RN  - 3K9958V90M (Ethanol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Animals
MH  - *Diet, High-Fat
MH  - Ethanol/*toxicity
MH  - Female
MH  - Fibrosis
MH  - Gene Expression Regulation
MH  - Gestational Age
MH  - Glomerulonephritis/*etiology/genetics/metabolism/pathology
MH  - Glucocorticoids/metabolism
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Kidney Glomerulus/*drug effects/metabolism/pathology
MH  - Male
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats, Wistar
MH  - Receptor, Angiotensin, Type 2/genetics/metabolism
MH  - Signal Transduction/*drug effects/genetics
OTO - NOTNLM
OT  - Angiotensin II type 2 receptor
OT  - Glomerulosclerosis
OT  - Glucocorticoid-insulin-like growth factor 1 axis
OT  - Podocyte epithelial-mesenchymal differentiation
OT  - Prenatal ethanol exposure
EDAT- 2019/12/08 06:00
MHDA- 2020/01/28 06:00
CRDT- 2019/12/08 06:00
PHST- 2019/07/25 00:00 [received]
PHST- 2019/11/23 00:00 [revised]
PHST- 2019/11/25 00:00 [accepted]
PHST- 2019/12/08 06:00 [pubmed]
PHST- 2020/01/28 06:00 [medline]
PHST- 2019/12/08 06:00 [entrez]
AID - S0378-4274(19)30383-2 [pii]
AID - 10.1016/j.toxlet.2019.11.026 [doi]
PST - ppublish
SO  - Toxicol Lett. 2020 Mar 15;321:44-53. doi: 10.1016/j.toxlet.2019.11.026. Epub 2019 
      Dec 4.