NONHUMAN PRIMATE MODEL OF STRETCH-INDUCED PRETERM LABOR

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 早产仍然是一个重大的经济和公共卫生负担，发病率正在上升。 我们的目标是建立一个非人灵长类动物（NHP）模型的拉伸诱导早产（PTL），以阐明如何机械拉伸是由子宫肌层和胎膜。 子宫牵拉通常是多胎妊娠中PTL发病的原因，在过去十年中，PTL占早产的15%，占早产率增加的50%。多胎妊娠的妇女可以通过早期超声识别，使其成为预防性干预的理想目标群体。统一的假设是，一种新的NHP模型的子宫拉伸将模仿人类拉伸诱导的PTL，并定义在这种类型的PTL的发病机制的起始和随后的事件。以前，我们已经定义了细胞内机制负责拉伸诱导表达的劳动力相关基因在体外，现在需要建立一个动物模型，在其中测试潜在的治疗干预措施。我们将利用一个成熟的长期插管NHP模型，通过扩张羊膜内球囊来创建牵张诱导的PTL。我们的NHP模型上级于PTL的低等哺乳动物模型，因为它与人类妊娠具有许多特征，包括胎盘结构和分娩的激素控制。该模型将允许在子宫伸展之前和期间对子宫肌层、母体和羊水室进行连续采样。如果要实现预防多胎妊娠PTL的干预措施，则必须在模拟人类状况的模型中阐明子宫牵张激活的途径。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Preterm birth remains a significant economic and public health burden and the incidence is rising. Our objective is to develop a nonhuman primate (NHP) model of stretch-induced preterm labor (PTL) to elucidate how mechanical stretch is sensed by the myometrium and fetal membranes. Uterine stretch is often responsible for the onset of PTL in multiple gestation, which accounts for 15% of preterm births and 50% of the increase in preterm birth rates over the last decade. Women with a multiple gestation can be identified by early ultrasound making them an ideal group to target for prophylactic interventions. The unifying hypothesis is that a novel NHP model of uterine stretch will emulate human stretch-induced PTL and define the initiating and subsequent events in the pathogenesis of this type of PTL. Previously, we have defined intracellular mechanisms responsible for stretch-induced expression of labor-associated genes in vitro and now need to establish an animal model in which to test potential therapeutic interventions. We will take advantage of a well-established chronically catheterized NHP model to create stretch-induced PTL by inflating an intra-amniotic balloon. Our NHP model is superior to lower mammalian models of PTL since it shares many features with human pregnancy including placental structure and hormonal control of parturition. This model will allow sequential sampling of myometrium, maternal, and amniotic fluid compartments before and during uterine stretch. If interventions to prevent PTL in multiple gestations are to be achieved, then pathways activated by uterine stretch must be elucidated in a model that emulates the human condition.