Submitted to: Teratology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/14/2001
Publication Date: 5/1/2002
Citation: BURGOON, J.M., SELHUB, J., NADEAU, M., SADLER, T.W. INVESTIGATION OF THE EFFECTS OF FOLATE DEFICIENCY ON EMBRYONIC DEVELOPMENT THROUGH THE ESTABLISHMENT OF A FOLATE DEFICIENT MOUSE MODEL. TERATOLOGY 65:219-227,2002. Interpretive Summary: The vitamin folic acid is involved in many vital processes in the body, including the synthesis of DNA, RNA proteins and other important functions called methylations. Other participants in these functions include vitamin B6 and vitamin B12. Because of these functions, low levels of these vitamins or inadequate intake could have adverse consequences particularly in the developing embryo. In this study we determined the effect of folic acid deficiency on the fetal development in mice models. We found that folate deficiency in female mice who became pregnant exhibited many of the characteristics of human folic acid deficiency, including low level of this vitamin in the blood and poor reproductive outcomes.
Technical Abstract: Folic acid (FA) has been shown to reduce the incidence of neural tube, craniofacial, and cardiovascular defects and low birth weight. The mechanism(s) by which the vitamin is effective, however, has not been determined. Therefore, a folic acid deficient mouse model was developed. To create a folic acid deficiency, ICR female mice were placed on a diet containing no FA and including 1% succinyl sulfathiazole (SS) for 4 weeks before mating. Control mice were fed diets with either: 1) FA and 1% SS [+SS only diet]; 2) FA [normal diet]; or 3) a breeding diet. Dams and fetuses were examined during various days of gestation. Blood analysis showed that by gestational day 18, plasma folate concentrations in the -FA+SS fed dams decreased to 1.13 ng/ml, a concentration approximately 3% of that in breeding diet fed dams (33.24 ng/ml) and 8% of that in +SS only/normal fed dams (13.59 ng/ml). RBC folate levels showed a similar decrease, whereas homocysteine concentrations increased. Reproductive outcome in the -FA+SS fed dams was poor with increased fetal deaths, decreased fetal weight, and delays in palate and heart development. Female mice fed a folic acid deficient diet and 1% succinyl sulfathiazole exhibited many of the characteristics common to human folic acid deficiency, including decreased plasma and RBC folate, increased plasma homocysteine, and poor reproductive outcomes. Thus, an excellent model has been created to investigate the mechanism(s) underlying the origin of birth defects related to folic acid deficiency. Copyright 2002 Wiley-Liss, Inc.