The promoter methylomes of monochorionic twin placentas reveal intrauterine growth restriction-specific variations in the methylation patterns
The promoter methylomes of monochorionic twin placentas reveal intrauterine growth restriction-specific variations in the methylation patterns
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DOI：
10.1038/srep20181
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发表时间：
2016-02-02
影响因子：
4.6
通讯作者：
Wang, Junwen
中科院分区：
文献类型：
--
作者：
He, Zhiming;Lu, Hanlin;Wang, Junwen
宫内生长受限（IUGR）影响胎儿，并在一生中产生许多病理后果。最近的研究表明，DNA甲基化的变化可能导致胎盘功能障碍，这可能与不良妊娠并发症有关。在这里，我们研究了7个选择性宫内生长限制（sIUGR）的单绒毛膜（MC）双胞胎胎盘的启动子甲基化组，以健康双胞胎为理想对照。我们的工作表明，IUGR胎盘共享具有独特的DNA低甲基化模式，甲基化变异优先发生在CpG岛海岸或非CpG岛启动子中。差异甲基化启动子可显著分离IUGR胎盘份额和健康胎盘份额。超高效液相色谱/串联质谱（UPLC-MS/MS）进一步证实了IUGR胎盘部分的全基因组DNA低甲基化和较低水平的羟甲基化状态。LRAT启动子和SLC19A1启动子（分别参与维生素A代谢和叶酸运输）以及EFS启动子的甲基化变化在另外12对患有sIUGR的MC双胞胎中得到了进一步验证。虽然LRAT、SLC19A1和EFS的表达没有受到影响，但我们仍然推测DNA甲基化和羟甲基化可能在子宫胎儿发育过程中发挥功能作用。
Intrauterine growth restriction (IUGR) affects the foetus and has a number of pathological consequences throughout life. Recent work has indicated that variations in DNA methylation might cause placental dysfunction, which may be associated with adverse pregnancy complications. Here, we investigated the promoter methylomes of placental shares from seven monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR) using the healthy twin as an ideal control. Our work demonstrated that the IUGR placental shares harboured a distinct DNA hypomethylation pattern and that the methylation variations preferentially occurred in CpG island shores or non-CpG island promoters. The differentially methylated promoters could significantly separate the IUGR placental shares from the healthy ones. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) further confirmed the genome-wide DNA hypomethylation and the lower level of hydroxymethylation statuses in the IUGR placental shares. The methylation variations of the LRAT and SLC19A1 promoters, which are involved in vitamin A metabolism and folate transportation, respectively, and the EFS promoter were further validated in an additional 12 pairs of MC twins with sIUGR. Although the expressions of LRAT, SLC19A1 and EFS were not affected, we still speculated that DNA methylation and hydroxymethylation might serve a functional role during in utero foetal development.