FETAL GROWTH AND THE INSULINLIKE GROWTH FACTOR AXIS

胎儿生长和类胰岛素生长因子轴

• 批准号: 3742060
• 负责人: ALICE F TARANTAL
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 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/3742060
• 关键词: Macaca fascicularis; Macaca mulatta; binding proteins; embryo /fetus; growth /development; insulinlike growth factor

Limited knowledge regarding the pathophysiology of intrauterine growth restriction (IUGR) emphasizes the need for studies which explore the mechanism(s) responsible for regulating fetal growth under both normal and compromised conditions. Studies were performed with the fetal monkey with the goal of characterizing normative baseline values for the insulin-like growth factors (IGF-I, IGF-II), which are key effectors of fetal growth and are modulated by serum carrier proteins (IGF binding proteins [IGFBPS]). IGF-I, IGF-II, and IGFBP-3 were studied in the rhesus (macaca mulatta) and long-tailed (macaca fascicularis) monkey fetus and dam during the second and third trimesters of pregnancy. Serial fetal blood samples were collected by cardiocentesis every 10 days from gestational day (gd) 90 - 160, and at 1 month postnatal age; maternal blood samples were collected at similar timepoints. Results indicated that maternal sera IGF-I and IGF-II did not change significantly whereas fetal concentrations of serum IGF-I and IGF-II increased approximately two-fold during the second to third trimesters. No significant differences were detected between the two species. Western-ligand blot analysis revealed predominant IGFBPS of 45-40 (IGFBP-3) and 28 KDA (IGF BP-1) in both maternal and fetal compartments, and western-immunoblot analysis using a specific antisera against IGFBP-3 indicated 45-40 and 28 KDA immunoreactive forms. Although IGF-I, IGF-II, and IGFBP-3 remained relatively unaffected in maternal sera during this period of gestation, fetal concentrations of IGF-Ii, IGF-II, and IGFBP-3 increased in a developmental profile similar to the human fetus. Future investigations with the fetal monkey will provide essential information on the role of the IGF axis in fetal growth in health and disease, which will be directly applicable to the human fetus under normal and growth-compromised conditions.

关于宫内生长的病理生理学知识有限 限制（IUGR）强调了探索研究的需求 在正常情况下，负责调节胎儿生长的机制 和损害条件。 使用胎儿猴进行研究 目的是表征该规范基线值 胰岛素样生长因子（IGF-I，IGF-II），这是 胎儿生长，由血清载体蛋白（IGF结合）调节 蛋白质[IGFBPS]）。在恒河猴中研究了IGF-I，IGF-II和IGFBP-3 （Macaca mulatta）和长尾（Macaca fascicularis）猴子胎儿和 在妊娠的第二和第三个三物种中的大坝。 连续胎儿 每10天从心脏穿刺术收集血液样本 妊娠日（GD）90-160，在产后1个月；母亲 在类似的时间点收集血液样本。 结果表明 母体血清IGF-I和IGF-II没有显着变化 血清IGF-I和IGF-II的胎儿浓度大约增加 在第二至第三个三重晶体中的两倍。 没有意义 在这两个物种之间检测到差异。西方配体印迹 分析揭示了45-40（IGFBP-3）和28 kDa（IGF）的主要IGFBPS（IGF） BP-1）在孕产妇和胎儿室以及西部免疫印迹 使用针对IGFBP-3的特定抗血清的分析表示为45-40，并且 28 kDa免疫反应性形式。 虽然IGF-I，IGF-II和IGFBP-3 在此期间，在母亲血清中仍然不受影响 妊娠，IGF-II，IGF-II和IGFBP-3的胎儿浓度增加 在类似于人类胎儿的发育特征中。 未来 胎儿猴的调查将提供基本信息 关于IGF轴在胎儿生长中的作用在健康和疾病中的作用， 在正常情况下将直接适用于人类胎儿 生长促进的条件。