Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems
Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems
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DOI：
10.1073/pnas.0504468103
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发表时间：
2005-12-27
影响因子：
11.1
通讯作者：
Fowden, A
中科院分区：
文献类型：
--
作者：
Constância, M;Angiolini, E;Fowden, A
哺乳动物的胎儿在妊娠期间依赖于母体通过胎盘提供的营养是独一无二的。母体对营养物质的供应和胎儿对营养物质的需求需要进行微调，以便胎儿沿着其遗传轨迹健康生长和发育。供需平衡的改变可能导致偏离这一轨道，对健康造成长期影响。我们先前已经表明，在缺乏印迹胎盘特异性Igf 2转录物（P0）的敲除中，胎盘的生长从妊娠早期受到损害，但胎儿生长正常，直到妊娠晚期，这表明胎盘的功能适应，以满足胎儿的需求。在这里，我们表明，胎盘运输的葡萄糖和氨基酸增加Igf 2 P0（+/-）空，这种上调运输发生，至少部分，通过增加表达的转运蛋白基因Slc 2a 3和Slc 38 a4，系统A氨基酸转运蛋白基因家族的印记成员。通过去除胎儿Igf 2基因降低胎儿需求，取消了这两个运输系统的上调，并降低了妊娠后期胎盘系统A氨基酸运输活性和Slc 38 a2的表达。我们的研究结果提供了直接的证据，胎盘可以通过调节特定的胎盘转运系统的表达来响应胎儿的需求信号。因此，印迹生长需求基因（Igf 2）和胎盘供应转运蛋白基因（Slc 38 a4，Slc 38 a2和Slc 2a 3）之间的串扰可能是哺乳动物发育过程中营养供应和需求的遗传控制的一个组成部分。
The mammalian fetus is unique in its dependence during gestation on the supply of maternal nutrients through the placenta. Maternal supply and fetal demand for nutrients need to be fine tuned for healthy growth and development of the fetus along its genetic trajectory. An altered balance between supply and demand can lead to deviations from this trajectory with long-term consequences for health. We have previously shown that in a knockout lacking the imprinted placental-specific Igf2 transcript (P0), growth of the placenta is compromised from early gestation but fetal growth is normal until late gestation, suggesting functional adaptation of the placenta to meet the fetal demands. Here, we show that placental transport of glucose and amino acids are increased in the Igf2 P0(+/-) null and that this up-regulation of transport occurs, at least in part, through increased expression of the transporter genes Slc2a3 and Slc38a4, the imprinted member of the System A amino acid transporter gene family. Decreasing fetal demand genetically by removal of fetal Igf2 abolished up-regulation of both transport systems and reduced placental System A amino acid transport activity and expression of Slc38a2 in late gestation. Our results provide direct evidence that the placenta can respond to fetal demand signals through regulation of expression of specific placental transport systems. Thus, crosstalk between an imprinted growth demand gene (Igf2) and placental supply transporter genes (Slc38a4, Slc38a2, and Slc2a3) may be a component of the genetic control of nutrient supply and demand during mammalian development.