Sunday, December 8, 2024
12/8/2024
PROJECT SUMMARY/ABSTRACT The overall objective of this study is to refine newly developed Optical Coherence Tomography-based imaging technology to investigate the role of cilia in the fallopian tube in vivo. Ciliopathies in women are associated with fertility disorders and ectopic pregnancies. Ciliated epithelial cells lining the lumen of the fallopian tube (oviduct) are known to play an essential role in reproduction. However, these very dynamic and complex reproductive processes have not been directly observed in vivo (yet), and the environment of the female reproductive tract is too complex to model. In particular, the dynamics of the fallopian tube cilia, their coordinated function, and their contribution to infertility are poorly understood, limiting the development of infertility treatments and assisted reproductive technology (ART). Here, we propose the first live dynamic investigation of cilia function in the mouse fallopian tube and the effect of ciliopathy on reproductive function. To do so, we will integrate technology development in functional optical coherence tomography (OCT), unique intravital imaging methods we recently established, and the mouse model of human ciliopathy with a fertility defect. This proposal will introduce a novel measure of coordinated ciliary dynamics, build a comprehensive visual understanding of the ciliary role in reproductive processes, and produce the first functional analysis of reproductive failures in a mouse model of ciliopathy toward a better understanding of the ciliopathy link to infertility. New methods developed in this study for dynamic cilia analysis can potentially be directly adapted for diagnostic purposes in clinics, and novel scientific findings in mice could be corroborated in humans, making a significant impact. Scientific Premise, Scientific Rigor, and Relevant Biological Variables: This proposal is clinically relevant and aims to fill a significant gap in the field of reproductive biology through highly innovative live imaging methods which we develop. Solid preliminary data and rigorous validations support all proposed experiments. “Sex as a biological variable” does not apply to our study design. Extensive details and references to our published protocols are provided to ensure that preliminary and proposed experiments can be replicated in other laboratories.
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