Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport
Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport
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DOI：
10.1113/jphysiol.2007.131185
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发表时间：
2007-06-15
影响因子：
5.5
通讯作者：
Jansson, Thomas
中科院分区：
文献类型：
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作者：
Ericsson, Anette;Saljo, Karin;Jansson, Thomas
对于患有 1 型糖尿病的孕妇，妊娠前三个月的血糖控制不佳是生下大胎儿的有力预测因素。然而，这种关联背后的机制尚不清楚。我们假设妊娠早期短暂的高血糖会导致（1）胎盘生长加快和（2）胎盘营养转运能力上调，从而导致足月胎儿过度生长。为了检验这一假设，怀孕大鼠在妊娠早期或晚期使用四种不同的方案腹腔注射葡萄糖（2 g kg(-1)，导致90分钟内血糖水平增加50-100%）或生理盐水（对照）：妊娠第10天（GD）1次（n = 5）注射1次，GD 10（n = 8-9）注射3次，GD 6次注射10 和 11 (n = 9-11) 或 GD 19 (n = 7-8) 上进行 3 次进样。多次注射间隔约4小时。随后，在 GD 21 上对动物进行了研究。妊娠早期注射 3 次葡萄糖，胎盘重量显着增加 10%，而妊娠早期注射 3 次葡萄糖（胎儿体重增加 9%，P < 0.05）和 6 次葡萄糖注射（7%，P = 0.05）均导致足月胎儿体重增加。 GD 10 注射一次葡萄糖或 GD 19 注射 3 次葡萄糖对胎盘或胎儿生长没有影响。在观察到胎儿胎盘生长变化的组中，我们测量了 GD 21 时清醒动物的胎盘系统 A 和葡萄糖转运活性，以及葡萄糖和氨基酸转运蛋白 GLUT1、GLUT3、SNAT2（系统 A）、LAT1 和 LAT 2（系统 L）的胎盘表达。妊娠早期注射 6 次葡萄糖，足月胎盘系统 A 转运下调（-33%，P < 0.05），而胎盘 mRNA 和蛋白质水平没有变化。未检测到母体代谢状态的长期变化。总之，我们证明妊娠早期短暂的高血糖足以增加接近足月的胎儿体重。相反，妊娠后期短暂的高血糖并不能刺激胎儿生长。胎儿生长加快可能是由于胎盘更大，胎盘更大，可以将更多的营养物质转移给胎儿。这些数据表明，妊娠早期母体代谢控制是整个妊娠剩余期间胎儿胎盘生长和胎盘功能的重要决定因素。我们推测，妊娠早期母体新陈代谢代表了胎盘做出反应的关键环境线索，以使胎儿生长速度与母亲的可用资源相匹配。
In pregnant women with type 1 diabetes, suboptimal glucose control in the first trimester is a strong predictor for giving birth to a large fetus. However, the mechanisms underlying this association are unknown. We hypothesized that transient hyperglycaemia in early pregnancy results in (1) increased placental growth and (2) an up-regulation of placental nutrient transport capacity, which leads to fetal overgrowth at term. In order to test this hypothesis, pregnant rats were given intraperitoneal injections of glucose (2 g kg(-1), resulting in a 50-100% increase in blood glucose level during 90 min) or saline (control) in either early or late gestation using four different protocols: one single injection on gestational day (GD) 10 (n = 5), three injections on GD 10 (n = 8-9), six injections on GD 10 and 11 (n = 9-11) or three injections on GD 19 (n = 7-8). Multiple injections were given approximately 4 h apart. Subsequently, animals were studied on GD 21. Three glucose injections in early pregnancy significantly increased placental weight by 10%, whereas fetal weight was found to be increased at term in response to both three (9% increase in fetal weight, P < 0.05) and six glucose injections (7%, P = 0.05) in early gestation. A single glucose injection on GD 10 or three injections of glucose on GD 19 had no effect on placental or fetal growth. In groups where a change in feto-placental growth was observed, we measured placental system A and glucose transport activity in the awake animals on GD 21 and placental expression of the glucose and amino acid transporters GLUT1, GLUT3, SNAT2 (system A), LAT1 and LAT 2 (system L). Placental system A transport at term was down-regulated by six glucose injections in early pregnancy (by -33%, P < 0.05), whereas placental mRNA and protein levels were unchanged. No long-term alterations in maternal metabolic status were detected. In conclusion, we demonstrate that transient hyperglycaemia in early pregnancy is sufficient to increase fetal weight close to term. In contrast, brief hyperglycaemia in late pregnancy did not stimulate fetal growth. Increased fetal growth may be explained by a larger placenta, which would allow for more nutrients to be transferred to the fetus. These data suggest that maternal metabolic control in early pregnancy is an important determinant for feto-placental growth and placental function throughout the remainder of gestation. We speculate that maternal metabolism in early pregnancy represents a key environmental cue to which the placenta responds in order to match fetal growth rate with the available resources of the mother.