Maternal Choline Supplementation during Normal Murine Pregnancy Alters the Placental Epigenome: Results of an Exploratory Study.
Maternal Choline Supplementation during Normal Murine Pregnancy Alters the Placental Epigenome: Results of an Exploratory Study.
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DOI：
10.3390/nu10040417
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发表时间：
2018-03-28
期刊：
影响因子：
5.9
通讯作者：
Caudill MA
中科院分区：
文献类型：
--
作者：
Kwan STC;King JH;Grenier JK;Yan J;Jiang X;Roberson MS;Caudill MA
胎盘表观基因组调节影响胎盘和胎儿发育的过程，并可能介导母体胆碱补充剂（MCS）对胎盘血管发育和营养输送的一些影响。作为先前在妊娠小鼠中进行的工作的延伸，本研究试图探索MCS对胎盘中各种表观遗传标记物的影响。从胚胎第15.5天从喂食1X或4X胆碱饮食的妊娠小鼠收集的胎盘中提取RNA和DNA，并进行全基因组测序程序或基于质谱的测定，以检查胎盘印迹基因表达，DNA甲基化模式和microRNA（miRNA）丰度。MCS在雌性胎盘中产生了4个印记基因（Ampd 3、Tfpi 2、Gatm和Aqp 1）的较高表达（倍数变化= 1.63-2.25），在雄性胎盘中产生了3个印记基因（Dcn、Qpct和Tnfrsf 23）的较低表达（倍数变化= 0.46-0.62）（两种性别的错误发现率（FDR）≤ 0.05）。这些基因的启动子区域的甲基化和整体胎盘DNA甲基化也受到影响（p ≤ 0.05）。此外，在4X胆碱胎盘中检测到miR-2137丰度较低（倍数变化= 0.3; Punadjusted = 2.05 × 10−4; FDR = 0.13），其靶基因表达较高（倍数变化= 1.25-3.92; p < 0.05）。这些数据表明，胎盘表观基因组对小鼠妊娠期间母体胆碱摄入量有反应，并可能介导一些先前描述的胆碱诱导的对胎盘和胎儿结局的影响。
The placental epigenome regulates processes that affect placental and fetal development, and could be mediating some of the reported effects of maternal choline supplementation (MCS) on placental vascular development and nutrient delivery. As an extension of work previously conducted in pregnant mice, the current study sought to explore the effects of MCS on various epigenetic markers in the placenta. RNA and DNA were extracted from placentas collected on embryonic day 15.5 from pregnant mice fed a 1X or 4X choline diet, and were subjected to genome-wide sequencing procedures or mass-spectrometry-based assays to examine placental imprinted gene expression, DNA methylation patterns, and microRNA (miRNA) abundance. MCS yielded a higher (fold change = 1.63–2.25) expression of four imprinted genes (Ampd3, Tfpi2, Gatm and Aqp1) in the female placentas and a lower (fold change = 0.46–0.62) expression of three imprinted genes (Dcn, Qpct and Tnfrsf23) in the male placentas (false discovery rate (FDR) ≤ 0.05 for both sexes). Methylation in the promoter regions of these genes and global placental DNA methylation were also affected (p ≤ 0.05). Additionally, a lower (fold change = 0.3; Punadjusted = 2.05 × 10−4; FDR = 0.13) abundance of miR-2137 and a higher (fold change = 1.25–3.92; p < 0.05) expression of its target genes were detected in the 4X choline placentas. These data demonstrate that the placental epigenome is responsive to maternal choline intake during murine pregnancy and likely mediates some of the previously described choline-induced effects on placental and fetal outcomes.
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作者：
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