{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:42:30Z","timestamp":1790106150057,"version":"4.0.1"},"reference-count":77,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,7,20]]},"abstract":"<jats:p>\n                    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% (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.01 vs. CT or CS) while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.01 vs. CT or CS). These changes were associated with &gt;\u00a025% decrease in the number of blood vessels in CD fetal hippocampus (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.01 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 (\n                    <jats:italic>Vegfc<\/jats:italic>\n                    ), 2.0-fold,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.01 vs. CT and angiopoietin 2 (\n                    <jats:italic>Angpt2<\/jats:italic>\n                    ), 2.1-fold, (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.01 vs. CT)). Similar increased expression was observed in NPC isolated from E14 fetal mouse brains and exposed to low (5\u00a0\u03bcM), CT (70\u00a0\u03bcM), or high choline (280\u00a0\u03bcM) media for 72\u00a0h (low choline caused a 9.7-fold increase in relative gene expression of\n                    <jats:italic>Vegfc<\/jats:italic>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.001 vs. CT and high) and a 3.4-fold increase in expression of\n                    <jats:italic>Angpt2<\/jats:italic>\n                    , (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05 vs. CT and high). ANGPT2 protein was increased 42.2% (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.01). Cytosine-phosphate-guanine dinucleotide islands in the proximity of the promoter areas of\n                    <jats:italic>Vegfc<\/jats:italic>\n                    and\n                    <jats:italic>Angpt2<\/jats:italic>\n                    were hypomethylated in low choline NPC compared to CT NPC (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.01). We conclude that maternal dietary choline intake alters angiogenesis in the developing fetal hippocampus.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0914328107","type":"journal-article","created":{"date-parts":[[2010,7,12]],"date-time":"2010-07-12T23:40:19Z","timestamp":1278978019000},"page":"12834-12839","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["Maternal dietary choline deficiency alters angiogenesis in fetal mouse hippocampus"],"prefix":"10.1073","volume":"107","author":[{"given":"Mihai G.","family":"Mehedint","sequence":"first","affiliation":[{"name":"University of North Carolina Nutrition Research Institute at Kannapolis, University of North Carolina at Chapel Hill, Kannapolis, NC 28081"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corneliu N.","family":"Craciunescu","sequence":"additional","affiliation":[{"name":"University of North Carolina Nutrition Research Institute at Kannapolis, University of North Carolina at Chapel Hill, Kannapolis, NC 28081"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Zeisel","sequence":"additional","affiliation":[{"name":"University of North Carolina Nutrition Research Institute at Kannapolis, University of North Carolina at Chapel Hill, Kannapolis, NC 28081"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,7,12]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"390","volume-title":"Dietary reference intakes for folate, thiamin, riboflavin, niacin, vitamin B12, panthothenic acid, biotin, and choline","year":"1998","unstructured":"Dietary reference intakes for folate, thiamin, riboflavin, niacin, vitamin B12, panthothenic acid, biotin, and choline (National Academy Press, Washington D.C.), pp. 390\u2013422 (1998)."},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.26.061505.111156"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.21.6.LB46-c"},{"key":"e_1_3_3_4_2","first-page":"435","article-title":"Evidence of saturable uptake mechanisms at maternal and fetal sides of the perfused human placenta by rapid paired-tracer dilution: studies with calcium and choline","volume":"8","author":"Sweiry JH","year":"1986","unstructured":"JH Sweiry, KR Page, CG Dacke, DR Abramovich, DL Yudilevich, Evidence of saturable uptake mechanisms at maternal and fetal sides of the perfused human placenta by rapid paired-tracer dilution: studies with calcium and choline. 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