title: Folic acid supplementation changes the fate of neural progenitors in mouse embryos of hyperglycemic and diabetic pregnancy.
abstract: Folic acid has been shown to decrease the incidence of neural tube defects (NTDs) in normal and hyperglycemic conditions, but the influence of folic acid on the development of central nervous system is not fully understood. Here, we aimed to explore the effects of folic acid, especially high dose of folic acid, on the characteristics of neural progenitors in embryos of hyperglycemic and diabetic mouse. Hyperglycemic and diabetic pregnant mice were given 3 mg/kg or 15 mg/kg folic acid from embryonic day 0.5 (E0.5) and were euthanased on E11.5, E13.5 or E18.5. The incidence of NTDs at E13.5 was counted. The proliferation, apoptosis and differentiation of neural progenitors and neuronal migration were determined using BrdU incorporation assay, TUNEL assay, immunofluorescence, Western blot and real-time reverse transcriptase polymerase chain reaction. Both normal and high doses of folic acid decreased the incidence of NTDs, promoted proliferation and reduced apoptosis of neuroepithelial cells in embryos of hyperglycemic and diabetic mice. Importantly, folic acid, especially at high dose, might affect the premature differentiation of neural progenitors in embryos of hyperglycemic and diabetic pregnancy. This may be attributed to changes of messenger RNA expression levels of some basic-helix-loop-helix transcription factors. In addition, folic acid might be involved in regulating neuronal migration in embryos of hyperglycemic and diabetic pregnancy. These findings suggest that periconceptional supplementation of folic acid, especially at high dose, may be a double-edged sword because it may result in undesirable outcomes affecting both the neuronal and glial differentiation in hyperglycemic and diabetic pregnancy.
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Qiuhuan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Shidou
authors.initials: S
authors.lastname: Zhao
authors.forename: Shangming
authors.initials: S
authors.lastname: Liu
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Fuwu
authors.initials: F
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.forename: Aijun
authors.initials: A
authors.lastname: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D019587:Dietary Supplements; D000089622:Doublecortin Domain Proteins; D004622:Embryo, Mammalian / Q000166:cytology*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006943:Hyperglycemia / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology*; D009479:Neuropeptides / Q000235:genetics; D011247:Pregnancy
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D005492:Folic Acid