SPONTANEOUS PLACENTAL INSUFFICIENCY--FETAL GROWTH RETARDATION MODEL

自发性胎盘功能不全--胎儿生长迟缓模型

• 批准号: 5212600
• 负责人: RANDALL B WILKENING
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5212600
• 关键词: aminoacid transport; dietary supplements; disease /disorder model; glucose transport; heat stimulus; hypoglycemia; injection /infusion; leucine; mother /embryo /fetus nutrition; nutrition related tag; placental transfer; pregnancy; prenatal growth disorder; sheep; stimulus interval; ultrasonography

Many forms of intrauterine growth retardation (IUGR) are likely to be the end result of a fetal metabolic adaptation to an imbalance between supply and demand of metabolic substrates. Recent studies in our ovine heat- stress model of placental insufficiency induced fetal growth retardation (PI-IUGR model) confirm our hypothesis that the marked IUGR characteristic to this model is associated with a placental transport limitation of multiple substrates, a metabolic adaptation which is different from that observed in other IUGR models. Our current hypotheses are that placental insufficiency occurs early in gestation in the PI-IUGR model and that the resulting placental amino acid transport limitation can be compensated for by long-term continuous maternal amino acid supplementation. The studies utilize our recently developed techniques of transabdominal ovine fetal ultrasonography to measure fetal growth in utero and our recently developed leucine two-tracer study design to compare the metabolism of this essential amino acid in the PI-IUGR fetus and placenta with the normal fetus by infusing L-[1-/14C]leucine into the fetus and L-[1- /13C]leucine is into the ewe. Specific aim 1 tests the hypothesis that decreased food intake does not contribute to IUGR of the PI-IUGR fetus. Specific aim 2 tests the hypothesis that placental insufficiency in the PI-IUGR model is irreversible by 0.6 term. Specific aims 3 and 4 test the hypothesis that leucine accretion by the PI-IUGR fetus and placenta will not increase after a 4-hour maternal amino acid infusion but will increase after a 30 day maternal amino acid infusion. Such studies provide an understanding of adaptative metabolic strategies in the IUGR fetus.

宫内内生长迟缓（IUGR）的多种形式可能是 胎儿代谢适应供应之间不平衡的最终结果 和代谢底物的需求。 我们的卵热的最新研究 胎盘不足引起的胎儿生长迟缓的压力模型 （PI-IUGR模型）证实我们的假设是标记的IUGR特征 该模型与胎盘运输限制有关 多个底物，一种代谢适应，与此不同 在其他IUGR模型中观察到。 我们目前的假设是胎盘 不足是在PI-IUGR模型的妊娠初期发生的，并且 由此产生的胎盘氨基酸运输限制可以得到补偿 通过长期连续的母体氨基酸补充。 研究 利用我们最近开发的腹卵巢胎儿技术 超声检查以测量子宫内胎儿生长和我们最近的 开发了亮氨酸两种追踪研究设计，以比较 PI-IUGR胎儿和胎盘中的这种必需氨基酸与 正常胎儿通过将l- [1-/14c]亮氨酸注入胎儿和l- [1- /13c]亮氨酸进入母羊。 特定目标1检验了以下假设 食物摄入量的降低不会导致Pi-iugr胎儿的IUGR。 特定目标2检验了以下假设 PI-IUGR模型在0.6项之前是不可逆的。 特定目标3和4测试 假设Pi-iugr胎儿和胎盘的亮氨酸会产生 4小时的母体氨基酸输注后不会增加，但会增加 经过30天的母体氨基酸输注。 这样的研究提供了 了解IUGR胎儿适应性代谢策略。