REGULATION OF FETAL-PLACENTAL DEVELOPMENT IN THE PRIMATE

灵长类动物胎儿胎盘发育的调节

基本信息

批准号：
7716055
负责人：
Eugene D. Albrecht
金额：
$ 26.36万
依托单位：
TEXAS BIOMEDICAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7716055
关键词：
11-beta-Hydroxysteroid Dehydrogenases Adrenal Glands Angiopoietin-1 Area Aromatase Inhibitors Biochemical Blood Vessels Cell Adhesion Molecules Communication Computer Retrieval of Information on Scientific Projects Database Development Ensure Enzymes Estradiol Estrogens Fetal Development Fetus Funding Goals Grant Growth Growth and Development function Homeostasis Human Hydrocortisone In Vitro Incidence Institution Integrins Knowledge Low Birth Weight Infant Modeling Molecular Neonatal Papio Patient currently pregnant Permeability Physiological Placenta Placentation Play Pregnancy Pregnant Women Prematurity of fetus Primates Regulation Research Research Personnel Research Proposals Resources Role Sodium-Hydrogen Antiporter Source Spiral Artery of the Endometrium Syncytiotrophoblast Testing United States National Institutes of Health Villous angiogenesis cytotrophoblast fetal improved in utero in vivo insight mortality neonatal morbidity programs trophoblast

11-beta-Hydroxysteroid Dehydrogenases Adrenal Glands Angiopoietin-1 Area Aromatase Inhibitors Biochemical Blood Vessels Cell Adhesion Molecules Communication Computer Retrieval of Information on Scientific Projects Database Development Ensure Enzymes Estradiol Estrogens Fetal Development Fetus Funding Goals Grant Growth Growth and Development function Homeostasis Human Hydrocortisone In Vitro Incidence Institution Integrins Knowledge Low Birth Weight Infant Modeling Molecular Neonatal Papio Patient currently pregnant Permeability Physiological Placenta Placentation Play Pregnancy Pregnant Women Prematurity of fetus Primates Regulation Research Research Personnel Research Proposals Resources Role Sodium-Hydrogen Antiporter Source Spiral Artery of the Endometrium Syncytiotrophoblast Testing United States National Institutes of Health Villous angiogenesis cytotrophoblast fetal improved in utero in vivo insight mortality neonatal morbidity programs trophoblast

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项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The high incidence of human neonatal morbidity and mortality associated with low birth weight and prematurity indicates need for more intensive study of the mechanisms underlying placental and fetal development. The long-term objective of this research proposal is to improve knowledge in this area by building on our previous in vivo studies in the pregnant baboon which demonstrate that estrogen plays an integrative role in placental-fetal communication by regulating maturation of the placenta and fetal adrenal gland. Study I will test the hypothesis that early in gestation estrogen stimulates vascular endothelial growth/permeability factor and/or angiopoietin-1/-2 formation by villous trophoblasts and thus placental angiogenesis, and concurrently regulates expression of integrins-adhesion molecules by extravillous cytotrophoblasts to restrain their invasion of uterine spiral arteries, and that via these actions estrogen coordinates angiogenesis and placentation to ensure fetal-placental development. The goals of Studies I and II are interwoven to test the hypothesis that estrogen acts on the newly vascularized placenta to regulate expression of sodium-hydrogen exchangers (NHE-1 and -3) and their regulatory factors in the syncytiotrophoblast, directly (NHE-1), and indirectly by regulating the 11beta-hydroxysteroid dehydrogenase enzymes and thus local cortisol levels (NHE-3) to ensure placental-fetal homeostasis. Studies II and III are integrated to test the hypothesis that estrogen acts on the fetal adrenal to promote development of the transitional zone and restrain growth and development of the fetal zone, and that this in utero programming governs adrenal maturation and function in adulthood. Molecular, histological, biochemical, and in vivo physiological parameters of placental trophoblast and fetal adrenal development will be determined in baboons in which estrogen levels are prematurely elevated by estradiol administration or suppressed by a specific aromatase inhibitor. The estrogen-depleted/-repleted pregnant baboon provides a unique primate model to investigate the effects of altered trophoblast function on fetal-neonatal maturation, studies which cannot be performed in pregnant women or with in vitro approaches. Completion of the proposed study will provide new insight into communication between the fetus and placenta and improve our knowledge of the regulation of fetal development and neonatal self-sufficiency.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。与低出生体重和早产相关的人类新生儿发病率和死亡率的高发生率表明需要对胎盘和胎儿发育的机制进行更深入的研究。该研究建议的长期目标是通过基于我们先前在孕妇狒狒的体内研究来改善该领域的知识，该研究表明雌激素通过调节胎盘和胎儿肾上腺的成熟来调节胎盘传播中起着综合作用。研究我将检验以下假说：妊娠早期雌激素刺激血管内皮生长/渗透率因子和/或羊皮细胞呈绒毛血管生成，从而形成胎盘血管生成，从而同时调节整合蛋白 - 粘附分子的表达，从而通过尿布蛋白质的表达来进行胎盘的表达，从而构成了螺旋层的表达。这些作用雌激素坐在血管生成和胎盘上，以确保胎儿质量发展。研究I和II的目标是交织的，以检验以下假说：雌激素作用于新近血管的胎盘上，以调节钠氢交换器（NHE-1和-3）的表达（NHE-1和-3）及其调节因子及其在依胞胞菌素成素中的调节因素，直接通过（NHE-1）（NHE-1）（NHE-1）和11 by hys andrys andrydrhys anddrrose derrosentrose derrosentros derrose derrose derrosiels androsAsiers androsAse。局部皮质醇水平（NHE-3），以确保胎盘 - 狂热稳态。研究II和III被整合以检验以下假设：雌激素作用于胎儿肾上腺以促进过渡区的发展并限制胎儿区域的生长和发展，并且在子宫编程中，这在成年中控制了肾上腺成熟和功能。分子，组织学，生化和体内生理参数和胎盘肾上腺发育的分子和体内生理参数将在狒狒中确定，在狒狒中，雌激素水平通过雌二醇给药过早地升高或被特定的芳香酶抑制剂抑制。缺乏雌激素的/重复的怀孕狒狒提供了一种独特的灵长类动物模型，以研究改变滋养细胞功能对胎儿 - 神经性成熟的影响，这是在孕妇或体外方法中无法进行的研究。拟议研究的完成将为胎儿和胎盘之间的交流提供新的见解，并提高我们对胎儿发育和新生儿自给自足的规范的了解。