PMID- 32134217
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20220531
IS  - 2472-1727 (Electronic)
VI  - 112
IP  - 7
DP  - 2020 Apr 15
TI  - Gestational exposure to valproic acid upregulates total Stat3 protein expression 
      while downregulating phosphorylated Stat3 in CD-1 mouse embryos with neural tube 
      defects.
PG  - 555-568
LID - 10.1002/bdr2.1666 [doi]
AB  - Valproic acid (VPA), a widely prescribed antiepileptic drug and an effective 
      treatment for psychiatric disorders, is teratogenic causing neural tube defects 
      (NTDs) and other defects in the exposed embryo. Signal transducer and activator 
      of transcription 3 (Stat3) is a transcription factor that is activated via 
      tyrosine phosphorylation. Stat3, as well as its active form (pYStat3), is 
      expressed during neural tube closure in murine development. This study 
      investigated the effects of in utero VPA exposure on embryonic Stat3 mRNA and 
      protein expression during the critical period of neural tube closure in CD-1 
      mouse embryos. Following the exposure of CD-1 pregnant mice to the teratogenic 
      dose of 400 mg/kg VPA or saline on gestational day (GD) 9, embryos were harvested 
      at 1, 3, 6, or 24 hr and on GD13. Stat3 mRNA levels remained unchanged at all 
      time points. Total Stat3 protein levels were significantly (p < .05) increased in 
      GD9 embryos at 1 and 6 hr post-exposure and in GD13 exposed nonexencephalic and 
      exencephalic embryo heads. In contrast, phosphorylated Stat3 levels were 
      significantly (p < .05) downregulated in GD9 embryos at the 3 and 6 hr time 
      points with an overall trend of downregulation in the GD10 and GD13 groups. Total 
      and phosphorylated Stat3 protein levels remained unchanged in nuclear extracts of 
      the exposed nonexencephalic and exencephalic GD13 embryo heads. The reported 
      significant downregulation of phosphorylated Stat3 levels suggests its possible 
      role in VPA-induced NTDs in mouse embryos.
CI  - (c) 2020 Wiley Periodicals, Inc.
FAU - Shafique, Sidra
AU  - Shafique S
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, K7L 3N6, Canada.
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, K7L 3N6, Canada.
AD  - School of Environmental Studies, Queen's University, Kingston, Ontario, K7L 3N6, 
      Canada.
LA  - eng
GR  - MPO115188/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200305
PL  - United States
TA  - Birth Defects Res
JT  - Birth defects research
JID - 101701004
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Teratogens)
RN  - 614OI1Z5WI (Valproic Acid)
SB  - IM
MH  - Animals
MH  - Female
MH  - Mice
MH  - *Neural Tube Defects/chemically induced
MH  - Neurulation
MH  - Pregnancy
MH  - STAT3 Transcription Factor/genetics
MH  - Teratogens/toxicity
MH  - *Valproic Acid/toxicity
OTO - NOTNLM
OT  - Valproic acid
OT  - mouse embryo
OT  - neural tube defects
OT  - phosphorylated Stat3
OT  - signal transducer and activator of transcription 3
OT  - teratogen
EDAT- 2020/03/07 06:00
MHDA- 2021/08/19 06:00
CRDT- 2020/03/06 06:00
PHST- 2020/01/31 00:00 [received]
PHST- 2020/02/19 00:00 [revised]
PHST- 2020/02/25 00:00 [accepted]
PHST- 2020/03/07 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2020/03/06 06:00 [entrez]
AID - 10.1002/bdr2.1666 [doi]
PST - ppublish
SO  - Birth Defects Res. 2020 Apr 15;112(7):555-568. doi: 10.1002/bdr2.1666. Epub 2020 
      Mar 5.