Developmental adaptations to increased fetal nutrient demand in mouse genetic models of Igf2-mediated overgrowth
Developmental adaptations to increased fetal nutrient demand in mouse genetic models of Igf2-mediated overgrowth
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DOI：
10.1096/fj.10-175273
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发表时间：
2011-05-01
期刊：
影响因子：
4.8
通讯作者：
Constancia, Miguel
中科院分区：
文献类型：
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作者：
Angiolini, Emily;Coan, Phillip M.;Constancia, Miguel
胎儿的健康发育取决于胎儿生长的遗传驱动力和母体通过胎盘提供营养的能力之间的最佳平衡。在过度生长的情况下，胎儿-胎盘信号对胎儿需求增加的反应一无所知。在这里，我们使用H19（Delta 13）小鼠模型研究了这个问题，该模型先前显示会导致Igf2水平升高。与野生型小鼠相比，H19（Delta 13）中的胎仔和胎盘重量在E19时分别增加了23%和45%。出乎意料的是，我们发现不成比例的大H19（Delta 13）胎盘转运的葡萄糖和系统A氨基酸减少了20 - 35%（每克胎盘），被动渗透性也有类似的降低，尽管与野生型小鼠相比，营养交换和理论扩散能力的表面积显著更大。关键转运蛋白基因Slc2a3和Slc38a4的表达降低了约20%。通过遗传性降低Igf2P0水平来减少H19（Delta 13）胎盘的过度生长，导致系统A活性的上调和胎儿过度生长的维持。我们的研究结果提供了直接的证据表明，大胎盘可以改变其营养转移能力，以调节胎儿的营养获取。我们的研究结果表明，胎儿-胎盘信号传导机制限制了对母体营养素的总需求。Angiolini，E.，Coan，P.M.，桑多维奇岛Iwajomo，O.H.，Peck，G.，伯顿，G.J.，Sibley，C.P.，Reik，W.，Fowden，A.L.，康斯坦西亚湾在Igf2介导的过度生长的小鼠遗传模型中对胎儿营养需求增加的发育适应。FASEB J.25，1737 - 1745（2011）。www.fasebj.org
The healthy development of the fetus depends on an optimal balance between fetal genetic drive for growth and the maternal ability to provide nutrients through the placenta. Nothing is known about fetal-placental signaling in response to increased fetal demand in the situation of overgrowth. Here, we examined this question using the H19(Delta 13) mouse model, shown previously to result in elevated levels of Igf2. Fetal and placental weights in H19(Delta 13) were increased by 23% and 45%, respectively, at E19, when compared with wild-type mice. Unexpectedly, we found that disproportionately large H19(Delta 13) placentas transport 20-35% less (per gram placenta) glucose and system A amino acids and have similar reductions in passive permeability, despite a significantly greater surface area for nutrient exchange and theoretical diffusion capacity compared with wild-type mice. Expression of key transporter genes Slc2a3 and Slc38a4 was reduced by similar to 20%. Decreasing the overgrowth of the H19(Delta 13) placenta by genetically reducing levels of Igf2P0 resulted in up-regulation of system A activity and maintenance of fetal overgrowth. Our results provide direct evidence that large placentas can modify their nutrient transfer capacity to regulate fetal nutrient acquisition. Our findings are indicative of fetal-placental signaling mechanisms that limit total demand for maternal nutrients.-Angiolini, E., Coan, P.M., Sandovici, I., Iwajomo, O.H., Peck, G., Burton, G.J., Sibley, C.P., Reik, W., Fowden, A.L., Constancia, M. Developmental adaptations to increased fetal nutrient demand in mouse genetic models of Igf2-mediated overgrowth. FASEB J. 25, 1737-1745 (2011). www.fasebj.org