IGFS IN TROPHOBLAST GROWTH AND FUNCTION

胎儿的生长依赖于胎盘。 的机制 肽生长因子影响正常的滋养层生长， 分化是这一过程的核心， 调节滋养层营养物质的运输。 特别是， 胎盘的氨基酸转运功能依赖于其 分化状态，以及控制运输的机制， 滋养层分化的各个阶段尚未确定。 一 一类肽类生长因子，胰岛素样生长因子（IGF-1 和IGF-2），可能在调节胎盘 生长、发育和功能，本项目的目标是 阐明IGFs影响滋养层细胞的步骤 增殖、分化和营养转运。 为这些 研究，正常人滋养层细胞和人BeWo的b30克隆 绒毛膜癌细胞系将被用作实验模型系统。 提出了四个目标： 1.将IGF受体的表达表征为以下功能： 滋养层分化 2.为了确定受体表达的极性， 面向胎儿的滋养层膜。 3.为了确定IGF-1和IGF-2对滋养层细胞增殖的影响， 分化和氨基酸转运。 4. 探讨胰岛素样生长因子结合蛋白在调节胰岛素样生长因子中的作用 在分化的滋养层中的活性。 这些研究的结果将为控制 滋养层的生长和发育，并将定义的步骤， 这对最佳的母体-胎儿氨基酸交换至关重要。 这些 观察应该增强我们对机制的理解 调节胎儿生长，从而有助于改善策略， 确保胎儿健康

Fetal growth is dependent on the placenta. The mechanisms by which peptide growth factors influence normal trophoblast growth and differentiation are central to this process, as are the pathways that regulate transport of nutrients across the trophoblast. In particular, the amino acid transport function of the placenta is dependent on its state of differentiation, and the mechanisms controlling transport at various stages of trophoblast differentiation have not been defined. One class of peptide growth factors, the insulin-like growth factors (IGF-1 and IGF-2), are likely to play major roles in regulating placental growth, development, and function, and the goals of this project are to elucidate the steps by which the IGFs influence trophoblast proliferation, differentiation, ad nutrient transport. For these studies, normal human trophoblasts and the b30 clone of the human BeWo choriocarcinoma cell line will be used as experimental model systems. Four aims are proposed: 1. To characterize the expression of IGF receptors as a function of trophoblast differentiation. 2. To determine the polarity of receptor expression on maternal- and fetal-facing trophoblast membranes. 3. To define the effects of IGF-1 and IGF-2 on trophoblast proliferation, differentiation, and amino acid transport. 4. To investigate the roles of IGF binding proteins in modulating IGF activity in the differentiating trophoblast. The results of these studies will provide insights into the control of trophoblast growth and development, and will define the steps that are crucial for optimal maternal-fetal exchange of amino acids. These observations should enhance our understanding of the mechanisms regulating fetal growth and thereby contribute to improved strategies to ensure fetal well-being.