PMID- 29753006
OWN - NLM
STAT- MEDLINE
DCOM- 20181231
LR  - 20181231
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 351
DP  - 2018 Jul 15
TI  - Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone 
      exposure on long bone development in fetal mice.
PG  - 12-20
LID - S0041-008X(18)30204-7 [pii]
LID - 10.1016/j.taap.2018.05.005 [doi]
AB  - Dexamethasone is routinely used for treating those mothers at risk for preterm 
      delivery. However, overexposure to exogenous glucocorticoids induces bone loss in 
      offspring, and the "critical window" and safe dose of this treatment are largely 
      unknown. In this study, we found that femoral length, and the length of the 
      primary ossification center were significantly reduced in fetal mice after 
      repeated prenatal dexamethasone exposure (PDE). Compared with single-course 
      exposure on gestational day (GD)15, newborn mice with repeated PDE (3 times, from 
      GD15 to 17) showed a significant decrease in femoral trabecular bone mass with 
      decreased trabecular number and thickness. For those newborn mice treated after 
      repeated PDE at different doses (0, 0.2, 0.8, and 1.2 mg/kg/d), the toxic effect 
      of dexamethasone on bone development was observed at 0.8 and 1.2 mg/kg/d. More 
      severe retardation in bone development was observed in the fetal mice after PDE 
      at 0.8 mg/kg/d during GD12-14, compared with that during GD15-17. Interestingly, 
      stronger toxic effects were observed in male newborn mice after PDE than were 
      observed in female newborn mice. In conclusion, PDE with multiple course, higher 
      dose, or exposure at an early stage of pregnancy have stronger toxic effects on 
      bone development of fetal mice.
CI  - Copyright (c) 2018 Elsevier Inc. 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, Xin
AU  - Zhao X
AD  - Department of Physiology, Basic Medical School of Wuhan University, No.185 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, Rui
AU  - Zhang R
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, No.185 
      Donghu Road, Wuhan, Hubei Province 430071, China.
FAU - Nie, Zaihui
AU  - Nie Z
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, No.185 
      Donghu Road, Wuhan, Hubei Province 430071, China.
FAU - Cheng, Xiang
AU  - Cheng X
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, No.185 
      Donghu Road, Wuhan, Hubei Province 430071, China.
FAU - Zhang, Xianrong
AU  - Zhang X
AD  - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical 
      University, No.1838, North of Guangzhou Avenue, Guangzhou, Guangdong Province 
      510515, China; Guangdong Provincial Key Laboratory of Bone and Cartilage 
      Regenerative Medicine, Nanfang Hospital, Southern Medical University, No.1838, 
      North of Guangzhou Avenue, Guangzhou, Guangdong Province 510515, China. 
      Electronic address: xianrongzh@smu.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, Wuhan University, No.185 Donghu Road, 
      Wuhan, Hubei Province 430071, China. Electronic address: wanghui19@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180509
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Glucocorticoids)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Bone Development/*drug effects/physiology
MH  - Dexamethasone/administration & dosage/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Femur/*drug effects/embryology/pathology
MH  - Fetal Development/*drug effects/physiology
MH  - Glucocorticoids/administration & dosage/*toxicity
MH  - Male
MH  - Mice
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/pathology
OTO - NOTNLM
OT  - Bone development
OT  - Course
OT  - Dexamethasone
OT  - Dose
OT  - Prenatal Exposure
OT  - Stage
EDAT- 2018/05/13 06:00
MHDA- 2019/01/01 06:00
CRDT- 2018/05/13 06:00
PHST- 2017/09/06 00:00 [received]
PHST- 2018/05/06 00:00 [revised]
PHST- 2018/05/07 00:00 [accepted]
PHST- 2018/05/13 06:00 [pubmed]
PHST- 2019/01/01 06:00 [medline]
PHST- 2018/05/13 06:00 [entrez]
AID - S0041-008X(18)30204-7 [pii]
AID - 10.1016/j.taap.2018.05.005 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2018 Jul 15;351:12-20. doi: 10.1016/j.taap.2018.05.005. 
      Epub 2018 May 9.