In vivo imaging platform for ectopic pregnancy research in mouse models

项目摘要/摘要 输卵管异位妊娠(TEP)是一种危及生命的生殖疾病，在中国，近2%的妊娠受到影响 发达国家。TEP的病因远未解决，没有办法设计预防措施和 早期诊断的策略很少。研究TEP是如何形成和发展的一直是极其困难的。 因为在健康怀孕期间接触人类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，一个受损的人 输卵管运输功能可导致胚胎滞留在输卵管内，这是TEP的先决条件，但 潜在的机制仍不清楚。缺乏能够评估卵母细胞/胚胎运输的成像技术 输卵管内胚胎滞留仍然是研究胚胎滞留的功能原因的关键障碍。事实上，正常的 哺乳动物输卵管中卵母细胞/胚胎的转运过程从未被可视化过。因此，当前 卵母细胞/胚胎运输过程的知识在很大程度上是从体外或体外实验推断出来的， 忽视了女性生殖系统的天然动力。考虑到输卵管环境 由于模型复杂，需要对卵母细胞/胚胎运输进行体内动态成像以了解 胚胎滞留在输卵管中的特定原因，这对于揭开TEP的病因是必不可少的。 本项目的目标是建立一种新型的活体成像平台，集成了对 卵母细胞/胚胎动力学和光遗传调控输卵管功能的详细过程 胚胎滞留在小鼠输卵管中。集成光学相干层析成像和双波长 将开发并示范用于纵向成像和成像制导的光遗传控制系统 在小鼠模型中操纵生殖过程。遗传和药理学方法将是 用来扰乱睫毛和肌肉功能，并利用体内成像平台，我们将调查 TEP中卵母细胞/胚胎运输过程受损并阐明胚胎残留的功能原因。 该项目的成功完成将使TEP研究向前迈进一大步，1)关键技术 进展和2)对TEP病因的新见解。

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.