In vivo imaging platform for ectopic pregnancy research in mouse models

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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.