FETAL ADAPTATION TO CHRONIC UTERINE BLOOD FLOW REDUCTION

胎儿宫内发育迟缓是围产儿的重要原因 发病率和死亡率。产妇的情况，导致减少 子宫胎盘血流一直与胎儿生长有关 智力迟缓。在这些情况下发生的胎儿新陈代谢适应 条件保证了胎儿的存活，但以生长为代价。这个 本研究的目的是阐明其作用机制。 负责影响胎儿生长发育的适应。这个 拟议的研究将检验以下假设：1)胎儿缺氧 由于子宫胎盘血流量减少会降低组织胰岛素 像生长因子I(IGF-I)一样的生物活性，这反过来将影响 选定组织(骨骼)中蛋白质合成和积累的减少 肌肉)，导致生长速度减速。2)IGF的变化- I生物活性和蛋白质代谢可以保留，至少部分地， 通过母体(以及胎儿)的氧气补充。3)输液 IGF-I进入胎儿后肢将导致蛋白质增加 骨骼肌组织中的合成。这些假说将得到检验。 用延迟性子宫胎盘血流减少模型 候选人培育的绵羊。胎儿线形的日常测量 在子宫胎盘血的14天之前和期间生长 流量减少，在此期间蛋白质合成的速度， 整个胎儿体内的分解、氧化和净堆积 与胎儿骨骼肌一样，将使用稳定的和 放射性示踪方法学。骨骼肌的新陈代谢将 使用活体胎儿后肢进行检查。 这些研究将提供对代谢的更广泛的理解。 有助于胎儿生长发育的过程 迟缓，从而可能刺激新的方法来 预防和治疗人类怀孕中的这种情况。

Intrauterine growth retardation is a significant cause of perinatal morbidity and mortality. Maternal conditions which results in reduced uteroplacental blood flow are consistently associated with fetal growth retardation. The fetal metabolic adaptations which occur under these conditions ensure survival of the fetus at he expense of growth. The purpose of the present investigation is to elucidate the mechanisms responsible for the adaptations which impact on fetal growth. The proposed studies will examine the following hypotheses: 1) fetal hypoxia due to uteroplacental blood flow reduction will decrease tissue insulin like growth factor I (IGF-I) bioactivity which in turn will effect a decrease in protein synthesis and accretion in selected tissues (skeletal muscle), resulting in deceleration in growth rate. 2) the changes in IGF- I bioactivity and protein metabolism can be reserved, at least in part, through maternal (and thereby fetal) oxygen supplementation. 3) infusion of IGF-I into the fetal hindlimb will result in increased protein synthesis in skeletal muscle tissue. These hypotheses will be tested using a model of prolonged uteroplacental blood flow reduction in the sheep developed by the candidate. Daily measurements of linear fetal growth will be made before and during 14 days of uteroplacental blood flow reduction during which time the rates of protein synthesis, breakdown, oxidation and net accretion in the whole fetal body as well as in fetal skeletal muscle will be determined using stable and radioactive tracer methodology. Skeletal muscle metabolism will be examined using an in vivo fetal hindlimb. These studies will provide a broader understanding of the metabolic processes which contribute to the development of fetal growth retardation, thereby possibly stimulating new approaches to the prevention and treatment of this condition in human pregnancies.