title: Maternal dietary choline deficiency alters angiogenesis in fetal mouse hippocampus.
abstract: We examined whether maternal dietary choline modulates angiogenesis in fetal brain. Pregnant C57BL/6 mice were fed either a choline-deficient (CD), control (CT), or choline-supplemented diet (CS) from days 12 to 17 (E12-17) of pregnancy and then fetal brains were studied. In CD fetal hippocampus, proliferation of endothelial cells (EC) was decreased by 32% (p < 0.01 vs. CT or CS) while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (p < 0.01 vs. CT or CS). These changes were associated with > 25% decrease in the number of blood vessels in CD fetal hippocampus (p < 0.01 vs. CT and CS), with no change in total cross-sectional area of these blood vessels. Expression of genes for the angiogenic signals derived from both endothelial and neuronal progenitor cells (NPC) was increased in CD fetal hippocampus VEGF C (Vegfc), 2.0-fold, p < 0.01 vs. CT and angiopoietin 2 (Angpt2), 2.1-fold, (p < 0.01 vs. CT)). Similar increased expression was observed in NPC isolated from E14 fetal mouse brains and exposed to low (5 microM), CT (70 microM), or high choline (280 microM) media for 72 h (low choline caused a 9.7-fold increase in relative gene expression of Vegfc (p < 0.001 vs. CT and high) and a 3.4-fold increase in expression of Angpt2, (p < 0.05 vs. CT and high). ANGPT2 protein was increased 42.2% (p < 0.01). Cytosine-phosphate-guanine dinucleotide islands in the proximity of the promoter areas of Vegfc and Angpt2 were hypomethylated in low choline NPC compared to CT NPC (p < 0.01). We conclude that maternal dietary choline intake alters angiogenesis in the developing fetal hippocampus.
authors.affiliation: University of North Carolina Nutrition Research Institute at Kannapolis, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Mehedint
authors.forename: Corneliu N
authors.initials: CN
authors.lastname: Craciunescu
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D002796:Choline Deficiency / Q000196:embryology* / Q000378:metabolism; D019175:DNA Methylation; D004032:Diet; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000098:blood supply* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D033261:Maternal-Fetal Relations; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000235:genetics; D009474:Neurons / Q000166:cytology; D010767:Phosphorylcholine / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D043925:Angiogenesis Inducing Agents; D012333:RNA, Messenger; D010767:Phosphorylcholine