Revealing Cilia Function in the Human Fallopian Tubes - SUMMARY The overall objective of this study is to advance our understanding of the role motile cilia play in the fallopian tubes (FTs) and to develop an endoscopic imaging system for in vivo clinical investigation of motile cilia function in FT pathologies. The FTs transport oocytes, sperm, embryos, and provide the environment for the complex and highly regulated process of fertilization and preimplantation development. Motile cilia, dynamic hair-like structures that cover the luminal epithelium of the FTs, are known to play an essential role in reproduction, and impaired cilia motility is associated with fertility disorders in women and reproductive pathologies, including endometriosis. However, because the cilia are microscopic structures and the FTs are positioned deep inside the female body, direct non-surgical imaging investigation has not previously been possible. Additionally, the female reproductive tract is significantly understudied compared to other organ systems. Despite the recognized and critical role of the motile cilia in the fallopian tubes, our understanding of their physiological function and dysfunction is extremely poor, limiting female reproductive disease management and development of infertility treatments. Through our unique integration of expertise in female fertility, endometriosis, imaging hardware and software, we will address this sore problem through three specific aims: Specific Aim 1: Define coordinated cilia function in healthy FTs and impairments in endometriosis. We will investigate cilia dynamics in freshly excised FT segments from premenopausal patients with and without endometriosis, using OCT, bright-field microscopy, and a miniature fiber bundle imager. This fundamental aim will reveal normal and altered FT cilia function and establish optimum imaging parameters. Specific Aim 2: Develop FT endoscopes with OCT and fiber bundle imaging, and test with intact specimens. Sub-mm diameter endoscopes that are clinically capable will be designed, built, and tested on intact reproductive tracts (uterus and FT). Algorithms for disentangling ciliary from probe and sample movement will be implemented, and the system readied for in vivo pilot studies. Specific Aim 3: Perform a pilot in vivo study to visualize cilia movement. Ten pre-menopausal patients undergoing hysterosalpingectomy will be recruited for endoscopic imaging of their FTs during a break in their standard of care surgery. The optimized endoscopes will be tested for their ability to enter the FT in vivo and quantify cilia movement in this challenging environment. Overall, we will advance the current understanding of normal FT cilia dynamics over the menstrual cycle, as well as alterations in the setting of endometriosis, and develop clinically-relevant imaging methods with promise for utility in diagnosing and monitoring FT dysfunction.
