PMID- 29902490
OWN - NLM
STAT- MEDLINE
DCOM- 20190411
LR  - 20190411
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 408
DP  - 2018 Sep 1
TI  - Decreased H3K9ac level of StAR mediated testicular dysplasia induced by prenatal 
      dexamethasone exposure in male offspring rats.
PG  - 1-10
LID - S0300-483X(18)30115-X [pii]
LID - 10.1016/j.tox.2018.06.005 [doi]
AB  - Prenatal dexamethasone exposure (PDE) could induce testicular developmental 
      toxicity in adults. The present study aims to confirm its intrauterine 
      origination, and to explore its potential intrauterine programming mechanism. The 
      pregnant rats were respectively injected subcutaneously with 0.2 and 0.8 mg/kg d 
      dexamethasone during gestational days (GD) 9 to 20. The testes and serum of 
      offspring rats were collected on GD20 and postnatal week (PW) 12. In vivo, PDE 
      significantly induced the abnormal testicular morphology in offspring from GD20 
      to PW12. Moreover, the serum and intratesticular testosterone levels and the 
      expression of testicular steroidogenic acute regulatory protein (StAR) were 
      reduced by PDE. The expression levels of glucocorticoid receptor (GR) and histone 
      deacetylase 7 (HDAC7) were increased in fetal testes. Furthermore, the histone 3 
      lysine 9 acetylation (H3K9ac) level in the StAR promoter was decreased by PDE 
      from GD20 to PW12. In vitro, mouse Leydig tumour cell line (MLTC-1) cells were 
      treated with dexamethasone (20, 100 and 500 nM), and the testosterone production 
      and StAR expression were reduced. Moreover, dexamethasone increased the 
      expression of HDAC7 by activating GR, which decreased the H3K9ac level in the 
      StAR promoter. Taken together, PDE caused testicular dysplasia before and after 
      birth in male offspring rats, and its mechanism was related to the 
      low-expressional programming of StAR mediated by decreasing H3K9ac level.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Liu, Min
AU  - Liu M
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Chen, Biao
AU  - Chen B
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China.
FAU - Pei, Linguo
AU  - Pei L
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Zou, Yunfei
AU  - Zou Y
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China; School of public health, Wannan Medical College, Wuhu, 241002, 
      Anhui, China.
FAU - Xiao, Hao
AU  - Xiao H
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China.
FAU - Zhou, Jin
AU  - Zhou J
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Chen, Liaobin
AU  - Chen L
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China. Electronic address: lbchen@whu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China; Department of Orthopedic Surgery, Zhongnan Hospital 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 - 20180611
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Glucocorticoids)
RN  - 0 (Histones)
RN  - 0 (Phosphoproteins)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 3XMK78S47O (Testosterone)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Acetylation
MH  - Age Factors
MH  - Animals
MH  - Cell Line, Tumor
MH  - Dexamethasone/*toxicity
MH  - Female
MH  - Gestational Age
MH  - Glucocorticoids/*toxicity
MH  - Histones/*metabolism
MH  - Leydig Cells/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Phosphoproteins/genetics/*metabolism
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Promoter Regions, Genetic
MH  - Protein Processing, Post-Translational/*drug effects
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects
MH  - Spermatogenesis/drug effects
MH  - Testis/*drug effects/metabolism/pathology
MH  - Testosterone/blood
OTO - NOTNLM
OT  - Histone acetylation
OT  - Intrauterine programming
OT  - Prenatal dexamethasone exposure
OT  - Steroidogenic acute regulatory protein (StAR)
OT  - Testes
EDAT- 2018/06/15 06:00
MHDA- 2019/04/12 06:00
CRDT- 2018/06/15 06:00
PHST- 2018/02/09 00:00 [received]
PHST- 2018/05/05 00:00 [revised]
PHST- 2018/06/10 00:00 [accepted]
PHST- 2018/06/15 06:00 [pubmed]
PHST- 2019/04/12 06:00 [medline]
PHST- 2018/06/15 06:00 [entrez]
AID - S0300-483X(18)30115-X [pii]
AID - 10.1016/j.tox.2018.06.005 [doi]
PST - ppublish
SO  - Toxicology. 2018 Sep 1;408:1-10. doi: 10.1016/j.tox.2018.06.005. Epub 2018 Jun 
      11.