Fetoplacental amino acid metabolism in IUGR pregnancies

IUGR妊娠中胎儿胎盘氨基酸代谢

• 批准号: 7072787
• 负责人: RANDALL B WILKENING
• 金额: $ 40.09万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7072787
• 关键词: aminoacid metabolism; aminoacid transport; embryo /fetus; embryo /fetus cell /tissue; gestational age; glutamates; glutamine; growth /development; histology; induced hypothermia; insulinlike growth factor; mammalian embryology; mass spectrometry; placenta; placental transfer; pregnancy; prenatal growth disorder; scanning electron microscopy; sheep; trophoblast; ultrasonography; umbilical cord

Intrauterine growth restriction (IUGR) is an important and relatively common problem in obstetrics. It contributes markedly to fetal and neonatal pathology and poor reproductive outcome, as well as adult pathology including a higher incidence of diabetes and hypertension. Fetal IUGR often results from impaired placental function and insufficient to meet demand for nutrients, and fetal adaptation to that placental function and insufficiency to meet fetal demands for nutrients, and fetal adaptation to that insufficiency. Studying the developing placenta and fetus is extremely important, therefore, in expanding our knowledge on fetomaternal interactions, prior to, and during the development of an IUGR fetus. We have developed an ovine model for IUGR that results from placental insufficiency (PI), created by exposure of pregnant ewes to a hypothermic environment during the period of maximal placental growth and development (40-120 dGa, term 147+/- 3 days). This model shares many of the physiological and biochemical characteristics documented in human IUGR pregnancies, including reduced fetal weight, asymmetrical growth, changes in glucose and amino acid metabolism, as well as velocimetry changes in the fetal circulation. The objective of this project is to determine the changes in placental vasculature, placental exchange surface area and fetoplacenta- interorgan exchange of essential and anionic amino acids during the period of maximal fetal growth (last third of pregnancy) in a model fo PI-IUGR. We propose that reductions in vilious exchange surface area and independent reductions in essential and anionic amino acid transporters contribute to the development of IUGR. We will test for differences in essential and anionic amino acid transport in vivo, as well as the expression and location of several transporters (y+, y+1, N and XAG) in vitro, in normal and IUGR placenta. We will report amino acid transport n terms of per unit tissue, and the expression data per surface area unit. We will also test for differences between normal and IUGR placentae for alterations in fetoplacental anionic amino acid transport and correlative interactions of members of the insulin-like growth factor (IGF) family in the development of the XAG system. The information provided by these studies is necessary to identify potential compensatory mechanisms in PI-IUGR pregnancies, which could lead to possible therapeutic approaches to improve placental-fetal nutrient exchange, placental growth and fetal growth.

宫内生长限制（IUGR）是产科中的重要且相对常见的问题。它显着促进胎儿和新生儿病理学，生殖结果不良，以及成人病理学，包括糖尿病和高血压的发病率更高。胎儿IUGR通常是由于胎盘功能受损而导致的，并且不足以满足营养需求，以及对胎盘功能的适应性和不足以满足胎儿对营养的需求以及胎儿适应这种不足的需求。因此，研究发育中的胎盘和胎儿非常重要，因此，在扩展我们对胎儿相互作用的知识，在IUGR胎儿的发展之前和过程中。我们已经为IUGR开发了一种卵巢模型，该模型是由胎盘功能不全（PI）导致的，该模型是在最大胎盘生长和发育期间通过孕妇母羊暴露于低温环境（40-120 DGA，术语147 +/- 3天）而产生的。 该模型具有人类IUGR妊娠中记录的许多生理和生化特征，包括胎儿体重降低，不对称生长，葡萄糖和氨基酸代谢的变化以及胎儿循环中的速度计变化。该项目的目的是确定胎盘交换表面积的变化，以及在最大胎儿生长期（妊娠的最后三分之一）中，在模型中，基本和阴离子氨基酸的胎儿间交换。我们提出，葡萄交换表面积的减少以及基本和阴离子氨基酸转运蛋白的独立减少有助于IUGR的发展。我们将测试体内必需和阴离子氨基酸转运的差异，以及在正常和IUGR胎盘中在体外的几个转运蛋白（Y+，Y+1，N和XAG）的表达和位置。我们将报告氨基酸转运N单位组织的n项和每个表面积单位的表达数据。我们还将测试正常和IUGR胎盘之间的差异，以改变XAG系统开发中胰岛素样生长因子（IGF）家族成员的胎儿阴离子氨基酸转运和相关性相互作用。这些研究提供的信息对于确定PI-IUGR妊娠的潜在补偿机制是必要的，这可能导致可能的治疗方法来改善胎盘养分养分的交换，胎盘生长和胎儿生长。