PMID- 29329878
OWN - NLM
STAT- MEDLINE
DCOM- 20180220
LR  - 20180220
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 286
DP  - 2018 Apr
TI  - Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone 
      exposure on fetal articular cartilage development.
PG  - 1-9
LID - S0378-4274(18)30008-0 [pii]
LID - 10.1016/j.toxlet.2018.01.008 [doi]
AB  - Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for 
      treating mothers at risk for preterm delivery. However, intrauterine overexposure 
      to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. 
      Also, the "critical window" and safe dose of this treatment are largely unknown. 
      This study investigated the course-, dose-, and stage-dependent toxic effects and 
      the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal 
      development and articular cartilage development. Pregnant mice (C57BL/6) received 
      subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day 
      (GD) 15 or once a day from GD 15 to 17, or received various doses of 
      dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received 
      dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy 
      (GD 15-17). Offspring's knee joints were harvested at birth for morphological 
      analyses and detection of gene expression. Repeated PDE significantly suppressed 
      fetal and articular cartilage development, which were characterized by decreased 
      body weight and body length, coarse articular cartilage surfaces, and reduced 
      gene and protein expression of Col2a1 and aggrecan. For those newborns treated 
      with repeated PDE at different doses, the toxic effects on fetal and articular 
      cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no 
      obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 
      0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on 
      fetal and articular cartilage development, compared with PDE during the late 
      embryonic stage. Detection of gene expression showed that the TGFbeta signaling 
      pathway in the articular cartilage was down-regulated after PDE. Taken together, 
      PDE induces fetal developmental toxicity and articular cartilage developmental 
      toxicity in a course-, dose-, and stage-dependent manner.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Chen, Ze
AU  - Chen Z
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, No.185 
      Donghu Road, Wuhan, Hubei Province, 430071, China.
FAU - Zhao, Zhe
AU  - Zhao Z
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, No.169 
      Donghu Road, Wuhan, Hubei Province, 430071, China.
FAU - Li, Yunzepeng
AU  - Li Y
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, No.185 
      Donghu Road, Wuhan, Hubei Province, 430071, China.
FAU - Zhang, Xingyu
AU  - Zhang X
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, No.185 
      Donghu Road, Wuhan, Hubei Province, 430071, China.
FAU - Li, Bin
AU  - Li B
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, No.169 
      Donghu Road, Wuhan, Hubei Province, 430071, China.
FAU - Chen, Liaobin
AU  - Chen L
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, No.169 
      Donghu Road, Wuhan, Hubei Province, 430071, China; Hubei Provincial Key 
      Laboratory of Developmentally Originated Disease, No.185 Donghu Road, Wuhan, 
      Hubei Province, 430071, China. Electronic address: lbchen@whu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, No.185 
      Donghu Road, Wuhan, Hubei Province, 430071, China; Hubei Provincial Key 
      Laboratory of Developmentally Originated Disease, No.185 Donghu Road, Wuhan, 
      Hubei Province, 430071, China. Electronic address: wanghui19@whu.edu.cn.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20180110
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Aggrecans)
RN  - 0 (Col2a1 protein, mouse)
RN  - 0 (Collagen Type II)
RN  - 0 (Glucocorticoids)
RN  - 0 (Transforming Growth Factor beta)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Aggrecans/genetics/metabolism
MH  - Animals
MH  - Cartilage, Articular/*drug effects/embryology/metabolism
MH  - Chondrogenesis/*drug effects
MH  - Collagen Type II/genetics/metabolism
MH  - Dexamethasone/administration & dosage/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fetus/*drug effects/metabolism/pathology
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Gestational Age
MH  - Glucocorticoids/administration & dosage/*toxicity
MH  - Maternal Exposure
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - Risk Assessment
MH  - Signal Transduction/drug effects
MH  - Transforming Growth Factor beta/genetics/metabolism
OTO - NOTNLM
OT  - Articular cartilage development
OT  - Developmental toxicity
OT  - Dexamethasone
OT  - Prenatal exposure
OT  - Transforming growth factor beta
EDAT- 2018/01/14 06:00
MHDA- 2018/02/21 06:00
CRDT- 2018/01/14 06:00
PHST- 2017/09/23 00:00 [received]
PHST- 2017/12/17 00:00 [revised]
PHST- 2018/01/09 00:00 [accepted]
PHST- 2018/01/14 06:00 [pubmed]
PHST- 2018/02/21 06:00 [medline]
PHST- 2018/01/14 06:00 [entrez]
AID - S0378-4274(18)30008-0 [pii]
AID - 10.1016/j.toxlet.2018.01.008 [doi]
PST - ppublish
SO  - Toxicol Lett. 2018 Apr;286:1-9. doi: 10.1016/j.toxlet.2018.01.008. Epub 2018 Jan 
      10.