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Research Communication

Folic Acid Supplementation of Pregnant Mice Suppresses Heat-Induced Neural Tube Defects in the Offspring^{1 ,2}

Jae-Ho Shin^*, and Kohei Shiota^*3

^* Department of Anatomy and Developmental Biology and Congenital Anomaly Research Center, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; National Institute of Toxicology Research, Korea Food and Drug Administration, Seoul 122-704, Korea

³To whom correspondence should be addressed: Telephone, +81-75-753-4341; Fax, +81-75-751-7529; E-mail, kshiota{at}med.kyoto-u.ac.jp.

Neural tube defects (NTD) are a group of malformations that result from the failure of the neural tube to close early in embryonic development and among the most common congenital malformations in humans. It has been reported that a substantial proportion of NTD in humans can be prevented by folic acid (FA) supplementation prior to conception and during the first months of pregnancy, and myo-inositol (MI) was shown to reduce the incidence of NTD in curly tail mice which are not prevented by FA. Brief maternal hyperthermia (HT) early in pregnancy has been implicated in NTD both in humans and laboratory animals, and anterior NTD including exencephaly and anencephaly are induced frequently when pregnant mice are exposed to HT. We examined the effect of FA or MI supplementation of pregnant mice on the occurrence of heat-induced NTD in the offspring. When pregnant mice were treated with FA (3 mg/kg) daily from gestational day (GD) 0.5 through GD 9.5 and heated at GD 8.5, the prevalence of NTD in the fetuses (26.6%) was significantly lower than the corresponding figure in the HT alone group (38.6%; P < 0.05). However we failed to detect the preventive effect of MI (500 mg/kg). The results of this study suggest that prenatal FA supplementation decreases HT-induced NTD in mice and sufficient FA intake during early pregnancy may be recommended to avoid the birth of malformed children.

KEY WORDS: • folic acid • myo-inositol • hyperthermia • neural tube defects • pregnancy • mice

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