Folic Acid Prevents Congenital Malformations in the Offspring of Diabetic Mice

Abstract

Abstract. 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.

Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study

“…Interestingly, it has been reported that folic acid reduces the incidence of NTDs in offspring in a mouse model of diabetes (Oyama et al, 2009). To date, however, the interaction between maternal genetic and environmental factors in determining the risk of NTDs has not been examined.…”

Resveratrol Prevents Impairment in Activation of Retinoic Acid Receptors and MAP Kinases in the Embryos of a Rodent Model of Diabetic Embryopathy

“…The development of almost all organs are affected by maternal diabetes; however, the central nervous system is comparatively more susceptible. [1][2][3] The majority of the diabetic embryopathy studies address mostly visible physical defects, especially neural tube defects (NTDs) and cardiac defects, in developing fetuses which occur in *11% of human cases and in *25% of animals in studies. 2,4 However, many studies have shown that some adult diseases might have their origin in fetal life due to the intrauterine environment during pregnancy.…”

Influences of olive leaf extract in the kidney of diabetic pregnant mice and their offspring

“…The hyperglycemia were induced by intraperitoneal injection of a single dose of streptozotocin (STZ, 240 mg/kg body weight, from Sigma chemical Co., St. Louis, Mo) diluted in phosphate-buffered saline pH 7.2 (Oyama, Sugimura, Murase, Uchida, Hayasaka, et al, 2009). After 7 days of injection, the plasma glucose concentration was measured from the tail vein.…”