PMID- 31661193
OWN - NLM
STAT- MEDLINE
DCOM- 20200825
LR  - 20200825
IS  - 2472-1727 (Electronic)
VI  - 111
IP  - 19
DP  - 2019 Nov 15
TI  - Characterizing the effects of in utero exposure to valproic acid on murine fetal 
      heart development.
PG  - 1551-1560
LID - 10.1002/bdr2.1610 [doi]
AB  - BACKGROUND: Recently, the use of the antiepileptic drug valproic acid (VPA) for 
      the treatment of psychiatric conditions has been on the rise. However, studies 
      have shown that in utero VPA exposure can affect embryonic development, including 
      being associated with congenital heart defects. One proposed mechanism of 
      VPA-initiated teratogenicity is the inhibition of histone deacetylase, which is 
      involved in the regulation of transcription factors that regulate cardiogenesis. 
      Myocyte enhancing factor 2C (Mef2c), a transcription factor involved in the 
      development of cardiac structure and cardiomyocyte differentiation, has been 
      shown to increase in response to in utero VPA exposure, associating with 
      contractile dysfunction and myocardial disorganization. METHODS: To characterize 
      the effects of VPA on murine heart development, pregnant CD-1 mice were dosed 
      with 400 mg/kg of VPA on gestational day (GD) 9. Using high-resolution 
      ultrasound, we examined the effects of VPA on cardiac contractile function on GD 
      14-18, with fetal hearts being harvested on GD 19 for histological analysis. 
      Lastly, we conducted quantitative real-time polymerase chain reaction to measure 
      the relative Mef2c gene expression in GD 16 murine hearts. RESULTS: We observed 
      structural anomalies at GD 19 in the hearts of VPA-treated mice. Additionally, 
      our results showed alterations in measures of cardiac contractility, with a 
      decrease or increase in cardiac contractile ability in VPA-treated mice depending 
      on the GD and measurement taken. CONCLUSIONS: These results further characterize 
      the effects of VPA on heart development and suggest that alterations in Mef2c 
      gene expression, at least on GD 16, do not mediate VPA-induced cardiotoxicity in 
      CD-1 mice.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Philbrook, Nicola A
AU  - Philbrook NA
FAU - Nikolovska, Ana
AU  - Nikolovska A
FAU - Maciver, Rebecca D
AU  - Maciver RD
FAU - Belanger, Christine L
AU  - Belanger CL
FAU - Winn, Louise M
AU  - Winn LM
AUID- ORCID: 0000-0003-1088-5538
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada.
AD  - School of Environmental Studies, Queen's University, Kingston, Ontario, Canada.
LA  - eng
PT  - Journal Article
DEP - 20191029
PL  - United States
TA  - Birth Defects Res
JT  - Birth defects research
JID - 101701004
RN  - 0 (MEF2 Transcription Factors)
RN  - 0 (Mef2c protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 614OI1Z5WI (Valproic Acid)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Embryonic Development/drug effects
MH  - Female
MH  - Fetal Development/*drug effects
MH  - Fetal Heart/*drug effects
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Heart Defects, Congenital/etiology/genetics
MH  - MEF2 Transcription Factors/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Myocytes, Cardiac/drug effects
MH  - Organogenesis/drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Transcription Factors/metabolism
MH  - Valproic Acid/*adverse effects/metabolism
OTO - NOTNLM
OT  - congenital heart defect
OT  - high-resolution ultrasound
OT  - valproic acid
EDAT- 2019/10/30 06:00
MHDA- 2020/08/26 06:00
CRDT- 2019/10/30 06:00
PHST- 2019/06/28 00:00 [received]
PHST- 2019/09/26 00:00 [revised]
PHST- 2019/10/09 00:00 [accepted]
PHST- 2019/10/30 06:00 [pubmed]
PHST- 2020/08/26 06:00 [medline]
PHST- 2019/10/30 06:00 [entrez]
AID - 10.1002/bdr2.1610 [doi]
PST - ppublish
SO  - Birth Defects Res. 2019 Nov 15;111(19):1551-1560. doi: 10.1002/bdr2.1610. Epub 
      2019 Oct 29.