A PRIMATE IN VITRO IMPLANTATION MODEL

灵长类动物体外植入模型

• 批准号: 8173150
• 负责人: THADDEUS G GOLOS
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173150
• 关键词: 3-Dimensional; Administrative Supplement; Adult; Cardiovascular system; Cell Communication; Cells; Computer Retrieval of Information on Scientific Projects Database; Conditioned Culture Media; Dendritic Cells; Development; Disease; Effector Cell; Embryo; Embryo Loss; Embryonic Development; Endocrine; Environment; Event; Extracellular Matrix; Failure; Fetal Growth; Fetal Growth Retardation; Funding; Grant; Growth Factor; Health; Hormones; Human; Human Development; Immune; In Vitro; Institution; Knowledge; Leukocytes; Macaca mulatta; Maternal-Fetal Exchange; Metabolic; Modeling; Molecular; Natural Killer Cells; Pathogenesis; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Primates; Regulation; Reproductive Physiology; Research; Research Personnel; Resources; Source; Time; United States National Institutes of Health; blastocyst; cytokine; fetal; implantation; improved; macrophage; monocyte; natural Blastocyst Implantation; parent grant; prenatal; research study; trophoblast

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. Objective: To develop new models with which we can investigate the early formation of the human placenta, as a major step in improving maternal-fetal health. One of the greatest gaps in our knowledge of human development is at the time of embryo implantation at the initiation of pregnancy, due to limitations on the experimental use of human embryos. In the parent grant, we proposed to adapt this paradigm and expand it to an in vitro implantation model with IVF-produced rhesus monkey embryos with 2 specific aims: to define trophoblast differentiation with rhesus monkey embryos in 3-dimensional extracellular matrix environments, and to determine the effects of 3-dimensional effector cells and selected growth factors on trophoblast differentiation. We have made substantial progress and have demonstrated that there is a significant impact of maternal monocytes, macrophages and NK cells on embryo development. In this administrative supplement, we will conduct three additional experiments: Experiment 1. To extend the study of maternal immune cell effects on embryo development to monocyte, macrophage and dendritic cell interactions with NK cells in regulation of cytokine secretion. Experiment 2. To define the effects of pregnancy hormones on leukocyte cytokine secretion. Experiment 3. To determine the effects of conditioned medium from monocytes, macrophages, dendritic cells and NK cells on cytokine secretion by cultured blastocysts. We will thus extend the significance of the parent grant and accelerate the development of new paradigms for studying primate-specific cellular and molecular events at embryo implantation. RELEVANCE TO HUMAN HEALTH: Failure to initiate appropriate early placental function (embryo attachment, trophoblast invasion, and initiation of hormone secretion) is likely to contribute to embryo loss in early pregnancy. Additionally, inappropriate placental development and abnormal establishment of the maternal-fetal interface are thought to contribute to the pathogenesis of diseases of later pregnancy (e.g., preeclampsia, fetal growth restriction). Finally, the intrauterine environment and prenatal fetal growth are now widely recognized to have a profound impact on adult endocrine, cardiovascular, metabolic and reproductive physiology. The development of new models with which we can investigate the early formation of the human placenta will be a major step in improving maternal-fetal health.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：开发新模型来研究人类胎盘的早期形成，作为改善母婴健康的重要一步。 由于人类胚胎实验使用的限制，我们对人类发育知识的最大差距之一是在怀孕初期的胚胎植入时期。在母基金中，我们建议采用这种范例并将其扩展到 IVF 产生的恒河猴胚胎的体外植入模型，其具体目标有两个：定义恒河猴胚胎在 3 维细胞外基质环境中的滋养层分化，以及确定 3 维效应细胞和选定的生长因子对滋养层分化的影响。 我们已经取得了实质性进展，并证明母体单核细胞、巨噬细胞和 NK 细胞对胚胎发育有显着影响。在这个行政补充中，我们将进行三个额外的实验： 实验1. 将母体免疫细胞对胚胎发育影响的研究扩展到单核细胞、巨噬细胞和树突状细胞与NK细胞在细胞因子分泌调节中的相互作用。 实验2. 确定妊娠激素对白细胞细胞因子分泌的影响。 实验3.确定来自单核细胞、巨噬细胞、树突状细胞和NK细胞的条件培养基对培养的囊胚分泌细胞因子的影响。 因此，我们将扩大父母资助的重要性，并加速开发用于研究胚胎植入时灵长类特异性细胞和分子事件的新范例。 与人类健康的相关性：未能启动适当的早期胎盘功能（胚胎附着、滋养层侵入和开始激素分泌）可能会导致妊娠早期胚胎丢失。此外，不适当的胎盘发育和母胎界面的异常建立被认为是导致妊娠后期疾病（例如先兆子痫、胎儿生长受限）的发病机制。最后，现在人们广泛认识到宫内环境和产前胎儿生长对成人内分泌、心血管、代谢和生殖生理学具有深远影响。开发新模型来研究人类胎盘的早期形成将是改善母婴健康的重要一步。