In vivo imaging platform for ectopic pregnancy research in mouse models

用于小鼠模型异位妊娠研究的体内成像平台

• 批准号: 10067861
• 负责人: Shang Wang
• 金额: $ 23.49万
• 依托单位: STEVENS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-10 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10067861
• 关键词: vivo; imaging; platform; ectopic; pregnancy

PROJECT SUMMARY/ABSTRACT Tubal ectopic pregnancy (tEP) is a life-threatening reproductive disorder affecting nearly 2% of pregnancies in developed countries. The etiology of tEP is far from resolved, leaving no way to design preventive measures and few strategies for early diagnosis. Investigating how a tEP forms and develops has been extremely difficult. Because it is unethical to access human oviduct (fallopian tube) during healthy pregnancies as the proper control, studying tEP in animal models is the only way to understand its etiology. It is currently believed that an impaired oviductal transporting function can lead to embryo retention in the oviduct as a prerequisite of tEP, yet the underlying mechanisms are still unclear. A lack of imaging technique able to assess the oocyte/embryo transport in the oviduct remains the key barrier to investigate the functional causes of embryo retention. In fact, the normal process of oocyte/embryo transport in a mammalian oviduct has never been visualized. As a result, current knowledge of the oocyte/embryo transport process was largely extrapolated from in vitro or ex vivo experiments, neglecting the native dynamics of the female reproductive system. Given that the oviductal environment is too complex to model, in vivo dynamic imaging of oocyte/embryo transport is greatly needed to understand the specific causes of embryo retention in the oviduct, which is essential to unravel the etiology of tEP. The goal of this project is to establish a novel in vivo imaging platform integrating longitudinal assessment of the oocyte/embryo dynamics and optogenetic control of the oviductal function to interrogate the detailed process of embryo retention in the mouse oviduct. An integrated optical coherence tomography and dual-wavelength optogenetic control system will be developed and demonstrated for longitudinal imaging and imaging-guided manipulation of the reproductive process in the mouse model. Genetic and pharmacological approaches will be utilized to disrupt the ciliary and muscular functions, and with the in vivo imaging platform, we will investigate the impaired oocyte/embryo transport process and elucidate the functional causes of embryo retentions in tEP. Successful completion of this project will bring a major step forward in tEP research with 1) a critical technological advancement and 2) new insights into the etiology of tEP.

项目总结/摘要 输卵管异位妊娠（tEP）是一种危及生命的生殖疾病，影响近2%的妊娠， 发达国家tEP的病因远未解决，无法设计预防措施， 早期诊断的策略很少。研究tEP如何形成和发展是非常困难的。 因为在健康怀孕期间进入人类输卵管（输卵管）作为适当的控制是不道德的， 在动物模型中研究tEP是了解其病因的唯一途径。目前认为， 输卵管运输功能可导致胚胎滞留在输卵管中，作为tEP的先决条件，然而， 潜在的机制仍不清楚。缺乏能够评估卵母细胞/胚胎转运的成像技术 输卵管中的膜仍然是研究胚胎滞留的功能性原因的关键屏障。事实上，正常的 卵母细胞/胚胎在哺乳动物输卵管中的运输过程从未被观察到。因此，目前 卵母细胞/胚胎转运过程的知识主要是从体外或离体实验中推断出来的， 忽视了女性生殖系统的自然动力学。考虑到输卵管环境太 由于模型复杂，因此非常需要卵母细胞/胚胎运输的体内动态成像来理解 输卵管中胚胎滞留的具体原因，这对于阐明tEP的病因至关重要。 本项目的目标是建立一种新型的体内成像平台， 卵母细胞/胚胎动力学和输卵管功能的光遗传学控制，以询问 胚胎滞留在小鼠输卵管中。一种集成光学相干层析成像和双波长 光遗传学控制系统将开发和演示纵向成像和成像引导 在小鼠模型中操纵生殖过程。遗传学和药理学方法将是 用于破坏纤毛和肌肉功能，并与体内成像平台，我们将调查 受损的卵母细胞/胚胎运输过程，并阐明胚胎滞留在tEP的功能性原因。 该项目的成功完成将使tEP研究向前迈出一大步，1）关键技术 进展和2）对tEP病因的新见解。