title: Folic acid supplementation during pregnancy protects against lipopolysaccharide-induced neural tube defects in mice.
abstract: Folic acid is a water-soluble B-complex vitamin. Increasing evidence demonstrates that physiological supply of folic acid during pregnancy prevents folic acid deficiency-related neural tube defects (NTDs). Previous studies showed that maternal lipopolysaccharide (LPS) exposure caused NTDs in rodents. The aim of this study was to investigate the effects of high-dose folic acid supplementation during pregnancy on LPS-induced NTDs. Pregnant mice were intraperitoneally injected with LPS (20 μg/kg/d) from gestational day (GD) 8 to GD12. As expected, a five-day LPS injection resulted in 19.96% of fetuses with NTDs. Interestingly, supplementation with folic acid (3mg/kg/d) during pregnancy significantly alleviated LPS-induced NTDs. Additionally, folic acid significantly attenuated LPS-induced fetal growth restriction and skeletal malformations. Additional experiment showed that folic acid attenuated LPS-induced glutathione (GSH) depletion in maternal liver and placentas. Moreover, folic acid significantly attenuated LPS-induced expression of placental MyD88. Additionally, folic acid inhibited LPS-induced c-Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor kappa B (NF-κB) activation in placentas. Correspondingly, folic acid significantly attenuated LPS-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in placentas, maternal serum and amniotic fluid. In conclusion, supplementation with high-dose folic acid during pregnancy protects against LPS-induced NTDs through its anti-inflammatory and anti-oxidative effects.
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei 230032, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei 230032, China; School of Nursing, Anhui Medical University, Hefei 230032, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.forename: Xu-Ting
authors.initials: XT
authors.lastname: Dong
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Shu-Xian
authors.initials: SX
authors.lastname: Wu
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D019587:Dietary Supplements; D005260:Female; D005317:Fetal Growth Retardation / Q000517:prevention & control; D005492:Folic Acid / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009436:Neural Tube Defects / Q000139:chemically induced / Q000517:prevention & control*; D011247:Pregnancy
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D005492:Folic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D005978:Glutathione
keywords: Developmental toxicity; Folic acid; Inflammation; Lipopolysaccharide; Neural tube defects; Oxidative stress