PMID- 25868845
OWN - NLM
STAT- MEDLINE
DCOM- 20150721
LR  - 20171116
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 285
IP  - 2
DP  - 2015 Jun 1
TI  - Increased DNA methylation of scavenger receptor class B type I contributes to 
      inhibitory effects of prenatal caffeine ingestion on cholesterol uptake and 
      steroidogenesis in fetal adrenals.
PG  - 89-97
LID - S0041-008X(15)00119-2 [pii]
LID - 10.1016/j.taap.2015.03.028 [doi]
AB  - Steroid hormones synthesized from cholesterol in the fetal adrenal are crucial 
      for fetal development. We have observed the inhibited fetal adrenal 
      corticosterone synthesis and increased intrauterine growth retardation (IUGR) 
      rate in rats under prenatal caffeine ingestion. The aim of this study is to 
      evaluate the effects of prenatal caffeine ingestion on cholesterol supply in 
      fetal adrenal steroidogenesis in rats and explore the underlying epigenetic 
      mechanisms. Pregnant Wistar rats were treated with 60 mg/kg . d caffeine from 
      gestational day (GD) 7 to GD17. Histological changes of fetal adrenals and 
      increased IUGR rates were observed in the caffeine group. There were 
      significantly decreased steroid hormone contents and cholesterol supply in 
      caffeine-treated fetal adrenals. Data from the gene expression array suggested 
      that prenatal caffeine ingestion caused increased expression of genes related to 
      DNA methylation and decreased expression of genes related to cholesterol uptake. 
      The following conjoint analysis of DNA methylation array with these 
      differentially expressed genes suggested that scavenger receptor class B type I 
      (SR-BI) may play an important role in caffeine-induced cholesterol supply 
      deficiency. Moreover, real-time RT-PCR and immunohistochemical detection 
      certified the inhibitory effects of caffeine on both mRNA expression and protein 
      expression of SR-BI in the fetal adrenal. And the increased DNA methylation 
      frequency in the proximal promoter of SR-BI was confirmed by bisulfite-sequencing 
      PCR. In conclusion, prenatal caffeine ingestion can induce DNA hypermethylation 
      of the SR-BI promoter in the rat fetal adrenal. These effects may lead to 
      decreased SR-BI expression and cholesterol uptake, which inhibits steroidogenesis 
      in the fetal adrenal.
CI  - Copyright (c) 2015 Elsevier Inc. 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 - Ma, Liang-Peng
AU  - Ma LP
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Wang, Lin-Long
AU  - Wang LL
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; Research Center of Food and Drug 
      Evaluation, Wuhan University, Wuhan 430071, China. Electronic address: 
      pingjie@whu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
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; Research Center of Food and Drug 
      Evaluation, Wuhan University, Wuhan 430071, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150411
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (CD36 Antigens)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Steroids)
RN  - 3G6A5W338E (Caffeine)
RN  - 4964P6T9RB (Aldosterone)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adrenal Glands/drug effects/*metabolism/pathology
MH  - Aldosterone/metabolism
MH  - Animals
MH  - CD36 Antigens/genetics/*metabolism
MH  - Caffeine/*toxicity
MH  - Central Nervous System Stimulants/*toxicity
MH  - Cholesterol/*metabolism
MH  - DNA Methylation/*physiology
MH  - Female
MH  - Fetal Growth Retardation/chemically induced/pathology
MH  - Fetus/drug effects/*metabolism
MH  - Hydrocortisone/metabolism
MH  - Male
MH  - Pregnancy
MH  - Rats
MH  - Rats, Wistar
MH  - Steroids/*metabolism
OTO - NOTNLM
OT  - Caffeine
OT  - Cholesterol
OT  - DNA methylation
OT  - Fetal adrenal
OT  - Scavenger receptor class B type I (SR-BI)
OT  - Steroid hormones
EDAT- 2015/04/15 06:00
MHDA- 2015/07/22 06:00
CRDT- 2015/04/15 06:00
PHST- 2014/11/30 00:00 [received]
PHST- 2015/03/19 00:00 [revised]
PHST- 2015/03/31 00:00 [accepted]
PHST- 2015/04/15 06:00 [entrez]
PHST- 2015/04/15 06:00 [pubmed]
PHST- 2015/07/22 06:00 [medline]
AID - S0041-008X(15)00119-2 [pii]
AID - 10.1016/j.taap.2015.03.028 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2015 Jun 1;285(2):89-97. doi: 10.1016/j.taap.2015.03.028. 
      Epub 2015 Apr 11.