一项小鼠研究发现，缺乏胆碱――细胞膜中的一种关键营养物质――的孕期饮食可能减少正在发育的胎儿大脑的血管形成。此前的研究已经确定胆碱调控着导致干细胞增殖的基因，而且还确定了饮食中缺乏胆碱可能减少小鼠胎儿大脑神经细胞的形成。为了检验胆碱是否能影响正在发育的胎儿的血管的形成，Steven Zeisel及其同事向怀孕的小鼠提供了缺乏胆碱的饮食和对照组饮食，然后检验了小鼠胎儿的大脑。这组科学家报告说，与对照组相比，缺乏胆碱的小鼠胎儿的海马区血管较少，这很可能与观察到的内皮细胞生产减少有关。此外，缺乏胆碱的饮食与调控新血管形成的两种生长因子浓度增加相关。这组作者提出，这些生长因子的增加可能通过导致内皮干细胞迅速分化（这会缩短干细胞增殖的时间）而减少新血管的形成。这组作者说，该研究可能对孕期护理产生影响，因为美国的许多孕妇的饮食含有的胆碱少于推荐剂量。
论文#09-14328: "Maternal dietary choline deficiency decreases angiogenesis in fetal mouse hippocampus," 作者 Mihai G. Mehedint, Corneliu N. Craciunescu和 Steven H. Zeisel
媒体联系人：Steven Zeisel，北卡罗来纳大学教堂山分校营养系
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC
电话：704-250-5003
电子邮件：steven_zeisel@unc.edu
Published online before print July 12, 2010, doi: 10.1073/pnas.0914328107
Maternal dietary choline deficiency alters angiogenesis in fetal mouse hippocampus
Mihai G. Mehedint, Corneliu N. Craciunescu, and Steven H. Zeisel1
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 μM), CT (70 μM), or high choline (280 μM) 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.
