NUTRITIONAL ROLE OF THE PLACENTA IN MALDEVELOPMENT

胎盘在发育不良中的营养作用

• 批准号: 3315447
• 负责人: ROBERT L. BRENT
• 金额: $ 14.21万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3315447
• 关键词: aminoacid transport; antibody formation; antibody specificity; antiserum; chorioallantoic membrane; clone cells; congenital disorders; developmental nutrition; dietary proteins; early embryonic stage; electrofocusing; embryo /fetus culture; enzyme linked immunosorbent assay; gel electrophoresis; gestational age; hybridomas; immunofluorescence technique; macromolecule; monoclonal antibody; mother /embryo /fetus nutrition; nutrition related tag; pinocytosis; placenta; placental transfer; prenatal growth disorder; radiotracer; scintillation spectrometry; surface antigens; teratogens; vitelline membrane

In the past, most studies dealing with the nutrition of the conceptus have been performed in the early or late stages of fetal development. A number of developments permit us to perform nutritional studies during the earliest period of organogenesis. These developments include the preparation of standardized embryotoxic and teratogenic antibodies, the development of rodent embryo culture methods and the quantitation of endocytosis into a reproducible methodology. Furthermore, the unique placentation in the rodent permits one to combine the above methodologies into experiments which can define several parameters of early embryonic nutrition, as well as determine the changing roles of the yolk sac and chorioplacenta throughout gestation. The specific aims of this program are (1) to study placental (yolk sac and chorioplacental) transport of small molecules and macromolecules (endocytosis) from early organogenesis to late gestation in normal and pathologic states utilizing in vitro (embryo culture, yolk sac culture) and in vivo techniques; 2) to study the two sources of amino acids for rat embryonic development, histiotrophic nutrition (intracellular digestion of exogenous proteins) versus the transport of exogenous free amino acids in the presence or absence of teratogenic antiserum; 3) to obtain endocytosis-reducing antibodies and/or teratogenic antibodies uncontaminated with non-specific gamma globulin by utilizing the monoclonal antibody technique; 4) to study the effect of antiserum prepared against primate yolk sac on primate development. These studies should permit the quantitation of the parameters of early embryonic nutrition and the evaluation of the role of placental dysfunction in embryopathology, as well as a reevaluation of the role of the yolk sac in early primate development. Furthermore, teratogenic antibodies provide a unique and important tool to study embryonic nutrition in the mammal during organogenesis and early fetal development. The uniqueness and importance of this research is related to several features: (1) the impact of protein and amino acid deprivation on the developing embryo can be studied both in vivo and in vitro; (2) the effect of malnutrition on the embryo can be studied without interfering with maternal nutrition; (3) these studies have clinical relevance because yolk sac dysfunction may be a contributing factor to human teratogenesis; and (4) quantifying yolk sac dysfunction which precedes teratogenesis may give us insight into the prevention of congenital malformations by either nutritional or pharmacological methods.

过去，大多数涉及孕体营养的研究都是 是在胎儿发育的早期或晚期进行的。 一个数字 的发展使我们能够在 器官发生的最早时期。 这些发展包括 标准化胚胎毒性和致畸抗体的制备， 啮齿动物胚胎培养方法的开发和定量 内吞作用转化为可重复的方法。 此外，独特的 啮齿类动物的胎盘植入允许将上述方法结合起来 进入可以定义早期胚胎的几个参数的实验 营养，以及确定卵黄囊和卵黄囊的变化作用 整个妊娠期间的绒毛膜胎盘。 该计划的具体目标是 (1) 研究胎盘（卵黄囊和绒毛膜胎盘）小分子的运输 从早期器官发生到晚期的分子和大分子（内吞作用） 利用体外（胚胎）在正常和病理状态下妊娠 培养、卵黄囊培养）和体内技术； 2）研究两者 大鼠胚胎发育、组织营养的氨基酸来源 营养（外源蛋白质的细胞内消化）与 在存在或不存在的情况下运输外源游离氨基酸 致畸抗血清； 3)获得减少内吞作用的抗体和/或 未受非特异性丙种球蛋白污染的致畸抗体 利用单克隆抗体技术； 4）研究效果 针对灵长类动物卵黄囊制备的抗血清对灵长类动物发育的影响。 这些 研究应允许对早期胚胎的参数进行定量 营养和胎盘功能障碍的作用评估 胚胎病理学，以及卵黄囊在胚胎病理学中的作用的重新评估 早期灵长类动物的发育。 此外，致畸抗体还提供 研究哺乳动物胚胎营养的独特而重要的工具 器官发生和早期胎儿发育。 独特性和重要性 这项研究涉及到几个特点：（1）蛋白质的影响 和氨基酸剥夺对发育中胚胎的影响可以在以下两个方面进行研究： 体内和体外； (2)营养不良对胚胎的影响 在不干扰母亲营养的情况下进行研究； (3) 这些研究 临床相关性，因为卵黄囊功能障碍可能是一个促成因素 人类致畸因素； (4) 量化卵黄囊功能障碍 发生在致畸之前的现象可能会让我们深入了解如何预防 通过营养或药物方法造成的先天性畸形。