PMID- 18781038
OWN - NLM
STAT- MEDLINE
DCOM- 20090421
LR  - 20190907
IS  - 1348-4540 (Electronic)
IS  - 0918-8959 (Linking)
VI  - 56
IP  - 1
DP  - 2009
TI  - Folic acid prevents congenital malformations in the offspring of diabetic mice.
PG  - 29-37
AB  - It is well known that maternal diabetes causes various congenital malformations. 
      Although there are many reports that folic acid (FA) administration in pregnancy 
      reduces the risk of birth defects including neural tube defects (NTDs), a precise 
      analysis on the preventive effect of FA against diabetic embryopathy has not been 
      done yet. In this study, we analyzed the preventive effects of FA on congenital 
      malformations including NTDs, cardiovascular, and skeletal malformations using a 
      diabetic mouse model. Female mice were rendered hyperglycemic by streptozotocin 
      and then mated. Pregnant diabetic mice were treated daily with FA (3 mg/kg body 
      weight) or saline between gestational days (GD) 6 and 10. On GD 18, fetuses were 
      examined for congenital malformations. FA did not affect plasma glucose levels. 
      In the DM control group, the incidence of NTDs, cardiovascular, and skeletal 
      malformations was 28.4%, 28.5%, and 29.7%, respectively. In the FA-treated group, 
      the corresponding proportions reduced to 6.0%, 2.5% and 12.5%, respectively. A 
      whole-mount TUNEL revealed an increased apoptosis in the hindbrain region of 
      embryos from DM control group on day 9.5, and the apoptosis was decreased by FA 
      treatment. Maternal plasma homocysteine levels on GD 9.5 were significantly 
      lowered in DM control group compared with those in non-DM group, and FA treatment 
      did not show a significant effect. These results indicate that FA is effective 
      for the prevention of various diabetic embryopathy including NTDs, 
      cardiovascular, and skeletal malformations, and suggested that this effect is 
      independent from homocysteine metabolism and possibly mediated by decreasing the 
      abnormal apoptosis during organogenesis.
FAU - Oyama, Kaori
AU  - Oyama K
AD  - Department of Genetics, Research Institute of Environmental Medicine, Nagoya 
      University, Japan.
FAU - Sugimura, Yoshihisa
AU  - Sugimura Y
FAU - Murase, Takashi
AU  - Murase T
FAU - Uchida, Akira
AU  - Uchida A
FAU - Hayasaka, Shizu
AU  - Hayasaka S
FAU - Oiso, Yutaka
AU  - Oiso Y
FAU - Murata, Yoshiharu
AU  - Murata Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080910
PL  - Japan
TA  - Endocr J
JT  - Endocrine journal
JID - 9313485
RN  - 0 (Blood Glucose)
RN  - 5W494URQ81 (Streptozocin)
RN  - 935E97BOY8 (Folic Acid)
SB  - IM
MH  - Animals
MH  - Blood Glucose/analysis
MH  - Body Weight
MH  - Congenital Abnormalities/etiology/*prevention & control
MH  - Diabetes Mellitus, Experimental/blood/complications/*drug therapy
MH  - Drug Evaluation, Preclinical
MH  - Embryo, Mammalian
MH  - Female
MH  - Fetal Weight/drug effects
MH  - Folic Acid/*therapeutic use
MH  - Male
MH  - Maternal-Fetal Exchange/drug effects
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Pregnancy
MH  - Pregnancy Outcome
MH  - *Pregnancy in Diabetics/blood/pathology/veterinary
MH  - Streptozocin
EDAT- 2008/09/11 09:00
MHDA- 2009/04/22 09:00
CRDT- 2008/09/11 09:00
PHST- 2008/09/11 09:00 [pubmed]
PHST- 2009/04/22 09:00 [medline]
PHST- 2008/09/11 09:00 [entrez]
AID - JST.JSTAGE/endocrj/K08E-180 [pii]
AID - 10.1507/endocrj.k08e-180 [doi]
PST - ppublish
SO  - Endocr J. 2009;56(1):29-37. doi: 10.1507/endocrj.k08e-180. Epub 2008 Sep 10.