Folic Acid Supplementation of Pregnant Mice Suppresses Heat-Induced Neural Tube Defects in the Offspring

Abstract

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.

Role of folic acid in chlorpyrifos induced teratogenicity in mice

“…Folic acid has been shown to reduce the incidence of neural tube defects caused by valproic acid (Dawson et al, 2006;Padmanabhan and Shafiullah, 2003) retinoic acid (Reynolds et al, 2003;Firat et al, 2005), ochratoxin A (Katagiri et al 2007), Fumonisin B1 (Sadler et al, 2002), ethanol (Yanaguita et al, 2008), arsenic (Gefrides et al, 2002) and hyperthermia (Shin and Shiota, 1999;Li et al, 2003). Its role in the prevention of other congenital defects has not yet been fully explored.…”

Immunohistochemical Study on the Fetal Rat Pituitary in Hyperthermia-Induced Exencephaly

“…The present study relied on a third method: fetal rats were subjected to hyperthermal stress in utero on day 9.5 of pregnancy. Hyperthermia at this early stage of fetal period is known to cause brain malformations including anencephaly or exencephaly in rats (Edwards, 1968(Edwards, , 1986Mirkes, 1985;Webster et al ., 1985;Aoyama and Yamashina, 1994) and mice (Webster and Edwards, 1984;Chernoff and Golden, 1988;Seller and Perkins-Cole, 1987;Shiota,1988;Shin and Shiota, 1999). The results reported in this article will show the evidence that hyperthermia-induced exencephaly causes marked growth retardation of the adrenal cortex and a decreased population of somatotropes in the adenohypophysis.…”

Evaluation of the levels of folate, vitamin B12, homocysteine and fluoride in the parents and the affected neonates with neural tube defect and their matched controls

“…The studies from the West have implicated maternal nutritional deficiency, especially of folate (and also vitamin B12 and zinc), as the likely cause of NTD [5][6][7][8][9][10][11]. Deficient folate levels may interfere with methylation processes and the process of closure of neural tube [9].…”

“…Deficient folate levels may interfere with methylation processes and the process of closure of neural tube [9]. Other studies have shown that folate metabolism is linked with that of homocysteine, methionine and cystathionine and that the micronutrients vitamin B12 and zinc are the co-factors in various reactions [10][11][12][13][14].…”