Division of Nutritional Sciences, Cornell University, 228 Savage Hall, Ithaca, NY 14853, USA.
FASEB J. 2013 Mar;27(3):1245-53. doi: 10.1096/fj.12-221648. Epub 2012 Nov 29.
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.
本研究探讨了母体胆碱摄入对人胎盘转录组的影响,特别关注其在调节胎盘血管功能中的作用。健康孕妇(n=26,妊娠 26-29 周)被随机分为 480mg 胆碱/d 组,该摄入量接近 450mg/d 的充足摄入量,或 930mg/d 组,持续 12 周。分娩时采集母体血液和胎盘样本。全基因组表达微阵列用于鉴定受母体胆碱摄入影响的胎盘基因和生物学过程。母体胆碱摄入影响了广泛的基因(n=166)和生物学过程(n=197),包括与血管功能相关的基因和过程。特别值得注意的是,在从 930mg/d 胆碱摄入组获得的胎盘组织中,抗血管生成因子和子痫前期风险标志物 fms 样酪氨酸激酶-1(sFLT1)下调了 30%(P=0.05)。在母体血液 sFLT1 蛋白浓度中也检测到类似的降低(P=0.04)。胆碱处理对 sFLT1 的下调在人滋养层细胞培养模型中得到了证实,可能与增强乙酰胆碱信号有关。这些发现表明,在母体饮食中补充额外的胆碱可能改善胎盘血管生成,并减轻子痫前期的一些病理前兆。