PMID- 26776438
OWN - NLM
STAT- MEDLINE
DCOM- 20160706
LR  - 20160208
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 340
DP  - 2016 Jan 18
TI  - DNA hypermethylation of acetoacetyl-CoA synthetase contributes to inhibited 
      cholesterol supply and steroidogenesis in fetal rat adrenals under prenatal 
      nicotine exposure.
PG  - 43-52
LID - S0300-483X(16)30002-6 [pii]
LID - 10.1016/j.tox.2016.01.002 [doi]
AB  - Prenatal nicotine exposure is a risk factor for intrauterine growth retardation 
      (IUGR). Steroid hormones synthesized from cholesterol in the fetal adrenal play 
      an important role in the fetal development. The aim of this study is to 
      investigate the effects of prenatal nicotine exposure on steroidogenesis in fetal 
      rat adrenals from the perspective of cholesterol supply and explore the 
      underlying epigenetic mechanisms. Pregnant Wistar rats were administered 1.0mg/kg 
      nicotine subcutaneously twice a day from gestational day (GD) 7 to GD17. The 
      results showed that prenatal nicotine exposure increased IUGR rates. Histological 
      changes, decreased steroid hormone concentrations and decreased cholesterol 
      supply were observed in nicotine-treated fetal adrenals. In the gene expression 
      array, the expression of genes regulating ketone metabolic process decreased in 
      nicotine-treated fetal adrenals. The following conjoint analysis of DNA 
      methylation array with these differentially expressed genes suggested that 
      acetoacetyl-CoA synthetase (AACS), the enzyme utilizing ketones for cholesterol 
      supply, may play an important role in nicotine-induced cholesterol supply 
      deficiency. Moreover, the decreased expression of AACS and increased DNA 
      methylation in the proximal promoter of AACS in the fetal adrenal was verified by 
      real-time reverse-transcription PCR (RT-PCR) and bisulfite sequencing PCR (BSP), 
      respectively. In conclusion, prenatal nicotine exposure can cause DNA 
      hypermethylation of the AACS promoter in the rat fetal adrenal. These changes may 
      result in decreased AACS expression and cholesterol supply, which inhibits 
      steroidogenesis in the fetal adrenal.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Wu, Dong-Mei
AU  - Wu DM
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - He, Zheng
AU  - He Z
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Chen, Ting
AU  - Chen T
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Liu, Yang
AU  - Liu Y
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Ma, Liang-Peng
AU  - Ma LP
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Ping, Jie
AU  - Ping J
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally 
      Originated Diseases, Wuhan 430071, China. Electronic address: pingjie@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160114
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (RNA, Messenger)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.16 (acetoacetyl-CoA synthetase)
SB  - IM
MH  - Adrenal Cortex Hormones/*biosynthesis
MH  - Adrenal Glands/*drug effects/embryology/enzymology
MH  - Animals
MH  - Cholesterol/*metabolism
MH  - Coenzyme A Ligases/genetics/*metabolism
MH  - DNA Methylation/*drug effects
MH  - Epigenesis, Genetic/*drug effects
MH  - Female
MH  - Fetal Growth Retardation/*chemically induced/enzymology/genetics
MH  - Gene Expression Regulation, Enzymologic
MH  - Gestational Age
MH  - Maternal Exposure
MH  - Nicotine/*toxicity
MH  - Nicotinic Agonists/*toxicity
MH  - Pregnancy
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Acetoacetyl-CoA synthetase (AACS)
OT  - Cholesterol
OT  - DNA methylation
OT  - Fetal adrenal
OT  - Nicotine
OT  - Steroid hormones
EDAT- 2016/01/19 06:00
MHDA- 2016/07/07 06:00
CRDT- 2016/01/19 06:00
PHST- 2015/11/22 00:00 [received]
PHST- 2015/12/28 00:00 [revised]
PHST- 2016/01/10 00:00 [accepted]
PHST- 2016/01/19 06:00 [entrez]
PHST- 2016/01/19 06:00 [pubmed]
PHST- 2016/07/07 06:00 [medline]
AID - S0300-483X(16)30002-6 [pii]
AID - 10.1016/j.tox.2016.01.002 [doi]
PST - ppublish
SO  - Toxicology. 2016 Jan 18;340:43-52. doi: 10.1016/j.tox.2016.01.002. Epub 2016 Jan 
      14.