Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice
Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice
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DOI：
10.1113/jphysiol.2009.181214
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发表时间：
2010-02-01
影响因子：
5.5
通讯作者：
Fowden, A. L.
中科院分区：
文献类型：
--
作者：
Coan, P. M.;Vaughan, O. R.;Fowden, A. L.
怀孕期间营养不良会降低出生体重，并对成人表型产生影响，从而影响预期寿命，但其对负责为胎儿生长提供营养的胎盘表型的影响在很大程度上仍不清楚。使用分子，形态和功能分析，胎盘表型进行了检查，在小鼠的饮食摄入量限制到80%的控制从怀孕第3天。在第16天，营养不良减少胎盘，但不是胎儿，与减少结合区体积和葡萄糖转运蛋白Slc2a1的胎盘表达的重量。在第19天，营养不良小鼠的胎盘和胎儿重量均减少（分别为对照组的91%和87%，P < 0.01），负责胎盘营养转移的胎盘带的体积和表面积也减少（分别为85%和86%，P < 0.03）。然而，相对于对照组，营养不良胎盘的示踪葡萄糖的单向母胎清除率保持不变，每克胎盘的甲基氨基异丁酸增加了166%（P < 0.005）。这与第19天时胎盘葡萄糖和A系统氨基酸转运蛋白Slc2a1和Slc38a2的表达分别增加18%和27%有关（P < 0.04）。在这两个年龄段，营养不良使胎盘特异性Igf2基因转录本的表达降低了35%（P < 0.01），尽管其启动子的甲基化不受影响。因此，当胎盘自身的生长受到母体营养不良的影响时，胎盘会进行调整，以帮助维持胎儿的生长。因此，胎盘表型对环境条件有反应，可能有助于预测子宫内编程的成人疾病的风险。
Undernutrition during pregnancy reduces birth weight and programmes adult phenotype with consequences for life expectancy, but its effects on the phenotype of the placenta, responsible for supplying nutrients for fetal growth, remain largely unknown. Using molecular, morphological and functional analyses, placental phenotype was examined in mice during restriction of dietary intake to 80% of control from day 3 of pregnancy. At day 16, undernutrition reduced placental, but not fetal, weight in association with decreased junctional zone volume and placental expression of glucose transporter Slc2a1. At day 19, both placental and fetal weights were reduced in undernourished mice (91% and 87% of control, respectively, P < 0.01), as were the volume and surface area of the labyrinthine zone responsible for placental nutrient transfer (85% and 86%, respectively, P < 0.03). However, unidirectional materno-fetal clearance of tracer glucose was maintained and methyl-aminoisobutyric acid increased 166% (P < 0.005) per gram of undernourished placenta, relative to controls. This was associated with an 18% and 27% increased placental expression of glucose and system A amino acid transporters Slc2a1 and Slc38a2, respectively, at day 19 (P < 0.04). At both ages, undernutrition decreased expression of the placental specific transcript of the Igf2 gene by 35% (P < 0.01), although methylation of its promoter was unaffected. The placenta, therefore, adapts to help maintain fetal growth when its own growth is compromised by maternal undernutrition. Consequently, placental phenotype is responsive to environmental conditions and may help predict the risk of adult disease programmed in utero.