The effect of a chronic maternal cortisol infusion on the late-gestation fetal sheep
The effect of a chronic maternal cortisol infusion on the late-gestation fetal sheep
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DOI：
10.1677/joe.0.1740027
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发表时间：
2002-07-01
影响因子：
4
通讯作者：
Harding, JE
中科院分区：
文献类型：
--
作者：
Jensen, EC;Gallaher, BW;Harding, JE
胎儿暴露于过量的母体糖皮质激素可改变胎儿的生长发育，从而为胎儿生长受损与出生后生理改变之间的联系提供了可能的机制。然而，暴露于过量的母体糖皮质激素对胎儿生理和宫内代谢的影响尚未被描述。因此，我们研究了慢性母体皮质醇输注对慢性插管胎羊胎儿生长、血压、代谢和内分泌状态的影响。从妊娠119天开始，给妊娠母羊注射氢化可的松(80 mg/d，n=6)或生理盐水(n=8)，连续10天。孕妇皮质醇输注使胎儿生长速度下降30%(腹围增长2.9±-0.3vs 1.8+/-0.4 mm/d，P=0.03)。母亲注射皮质醇使胎儿心脏重量相对于体重增加了15%，左、右室室壁厚度分别增加了30%和50%。脾重量减轻30%，胎盘重量减轻25%。在母亲注射皮质醇的过程中，胎儿血压增加了大约10毫米汞柱(20%)。母亲注射皮质醇并没有改变氨基氮浓度。然而，母亲注射皮质醇后，母亲乳酸浓度增加了80%，胎儿乳酸浓度增加了74%，母亲和胎儿尿素浓度都增加了40%。在母亲皮质醇注射结束时，孕妇循环中的胰岛素样生长因子结合蛋白(IGFBP)-3水平增加了20%。在皮质醇输注过程中，胎儿IGF-I浓度下降，且胎儿IGFBP-1浓度与胎儿体重呈负相关(r=-0.76，P=0.02)。我们认为，即使母亲皮质醇水平轻微升高，也会影响胎儿的生长发育、心血管功能、代谢和内分泌状态，这可能会产生长期影响。
Exposure of the fetus to excess maternal glucocorticoids has been postulated to alter fetal growth and development, and thus provide a possible mechanism for the link between impaired fetal growth and altered postnatal physiology. However, the effects of exposure to excess maternal glucocorticoids on fetal physiology and metabolism in utero have not been described. We therefore studied the effects of chronic maternal cortisol infusion on fetal growth, blood pressure, metabolism and endocrine status in chronically catheterised fetal sheep. We infused hydrocortisone (80 mg/day, n = 6) or saline (n = 8) for 10 days into the pregnant ewes beginning at 119 days of gestation. Maternal cortisol infusion reduced fetal growth rate by 30% (girth increment 2.9 +/- 0.3 vs 1.8 +/- 0.4 mm/ day, P=0.03). Maternal cortisol infusion increased fetal heart weight by 15% relative to body weight and increased ventricular wall thickness by 30% in the left and 50% in the right ventricle. The weight of the spleen was reduced by 30% and placental weight reduced by 25%. Fetal blood pressure increased by approximately 10 mmHg (20%) during maternal cortisol infusion.Maternal cortisol infusion did not alter amino-nitrogen concentrations. However, maternal lactate concentrations increased by 80% and fetal lactate concentrations increased by 74% with maternal cortisol infusion, and both maternal and fetal urea concentrations increased by 40%. Circulating maternal IGF-binding protein (IGFBP)-3 levels had increased by 20% by the end of the maternal cortisol infusion. Fetal IGF-I concentrations decreased during cortisol infusion and fetal IGFBP-1 concentrations were negatively correlated with fetal weight (r= - 0.76, P=0.02).We conclude that even a modest elevation of maternal cortisol levels affects fetal growth, cardiovascular function, metabolism and endocrine status which may have long-term consequences.