Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction.
Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction.
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DOI：
10.1038/ng.3699
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发表时间：
2016-12
期刊：
影响因子：
30.8
通讯作者：
Charalambous M
中科院分区：
文献类型：
--
作者：
Cleaton MA;Dent CL;Howard M;Corish JA;Gutteridge I;Sovio U;Gaccioli F;Takahashi N;Bauer SR;Charnock-Jones DS;Powell TL;Smith GC;Ferguson-Smith AC;Charalambous M
怀孕是一种高代谢需求的状态。禁食将代谢转向脂肪酸氧化，孕妇的禁食反应发生得比非孕妇快得多。印迹型δ样同源1基因（DLK1）的产物是一种内分泌信号分子，在妊娠后期在母体循环中达到高浓度。通过使用缺失Dlk1的小鼠模型，我们发现胎儿是母体循环Dlk1的来源。在缺乏胎源性DLK1的情况下，母体的禁食反应受损。此外，我们发现母体循环DLK1水平可以预测小鼠的胚胎质量，并可以在人类队列中区分健康小胎龄婴儿（SGA）和病理性小婴儿。因此，测定母体血液中的DLK1可能是诊断与DLK1表达受损相关的人类疾病、预测宫内生长不良和妊娠并发症的一种有价值的方法。
Pregnancy is a state of high metabolic demand. Fasting diverts metabolism to fatty acid oxidation, and the fasted response occurs much more rapidly in pregnant women than in the non-pregnant state. The product of the imprinted Delta-like homologue 1 gene (DLK1) is an endocrine signaling molecule that reaches a high concentration in the maternal circulation during late pregnancy. By utilising murine models with deleted Dlk1 we show that the fetus is the source of maternal circulating DLK1. In the absence of fetally-derived DLK1, the maternal fasting response is impaired. Furthermore, we found that maternal circulating DLK1 levels predict embryonic mass in mice and can differentiate healthy small for gestational age (SGA) from pathologically small infants in a human cohort. Therefore measurement of DLK1 in maternal blood may be a valuable method for diagnosing human disorders associated with impaired DLK1 expression, and to predict poor intrauterine growth and complications of pregnancy.