title: A higher maternal choline intake among third-trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms-like tyrosine kinase-1 (sFLT1).
abstract: This study investigated the influence of maternal choline intake on the human placental transcriptome, with a special interest in its role in modulating placental vascular function. Healthy pregnant women (n=26, wk 26-29 gestation) were randomized to 480 mg choline/d, an intake level approximating the adequate intake of 450 mg/d, or 930 mg/d for 12 wk. Maternal blood and placental samples were retrieved at delivery. Whole genome expression microarrays were used to identify placental genes and biological processes impacted by maternal choline intake. Maternal choline intake influenced a wide array of genes (n=166) and biological processes (n=197), including those related to vascular function. Of special interest was the 30% down-regulation (P=0.05) of the antiangiogenic factor and preeclampsia risk marker fms-like tyrosine kinase-1 (sFLT1) in the placenta tissues obtained from the 930 vs. 480 mg/d choline intake group. Similar decreases (P=0.04) were detected in maternal blood sFLT1 protein concentrations. The down-regulation of sFLT1 by choline treatment was confirmed in a human trophoblast cell culture model and may be related to enhanced acetylcholine signaling. These findings indicate that supplementing the maternal diet with extra choline may improve placental angiogenesis and mitigate some of the pathological antecedents of preeclampsia.
authors.affiliation: Division of Nutritional Sciences, Cornell University, 228 Savage Hall, Ithaca, NY 14853, USA.
authors.forename: Xinyin
authors.initials: X
authors.lastname: Jiang
authors.forename: Haim Y
authors.initials: HY
authors.lastname: Bar
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Sara
authors.initials: S
authors.lastname: Jones
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Brannon
authors.forename: Allyson A
authors.initials: AA
authors.lastname: West
authors.forename: Cydne A
authors.initials: CA
authors.lastname: Perry
authors.forename: Anita
authors.initials: A
authors.lastname: Ganti
authors.forename: Eva
authors.initials: E
authors.lastname: Pressman
authors.forename: Srisatish
authors.initials: S
authors.lastname: Devapatla
authors.forename: Francoise
authors.initials: F
authors.lastname: Vermeylen
authors.forename: Martin T
authors.initials: MT
authors.lastname: Wells
authors.forename: Marie A
authors.initials: MA
authors.lastname: Caudill
mesh_terms: D000109:Acetylcholine / Q000097:blood; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D002794:Choline / Q000008:administration & dosage*; D019587:Dietary Supplements; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D055106:Genome-Wide Association Study; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011225:Pre-Eclampsia / Q000097:blood; D011247:Pregnancy / Q000097:blood*; D011263:Pregnancy Trimester, Third / Q000097:blood*; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D047929:Term Birth / Q000097:blood; D059467:Transcriptome / Q000187:drug effects / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D002794:Choline; D000109:Acetylcholine