In vivo imaging of mammalian fertilization

PROJECT SUMMARY/ABSTRACT The overall objective of this study is to develop a novel imaging technology to directly observe and better understand multiple aspects of fertilization within the mouse fallopian tube in vivo. This study is aligned with the NIH mission in Woman’s Health Research established across all NIH Institutes and Centers “to advance rigorous research that is relevant to the health of women”. The ovulation, fertilization, and pre-implantation pregnancy are fundamental processes of clinical importance. However, because mammalian reproductive processes take place deep inside the body, our understanding of cellular and molecular mechanisms driving reproduction is based on the histology of extracted organs, low- resolution visualizations, and extrapolation from invertebrate animal models (e.g., sea urchin). The dynamic environment of the female reproductive tract is too complex to model, and understanding the interplay between the oviduct eggs, sperm, and the oviduct environment based on in vitro data without direct observation is not feasible. Therefore, much of our knowledge regarding the dynamics of fertilization and oocyte/embryo transfer in vivo is based on assumptions thereby limiting the development of infertility treatments and assisted reproductive technology (ART). By integrating expertise in live functional optical imaging and reproductive biology, we established a unique project investigating multiple aspects of fertilization in vivo within the mouse fallopian tube with functional optical coherence tomography (OCT). We performed the first in vivo tracking of oocytes and embryos within the fallopian tube and made discoveries that question current views in the reproductive field, setting a foundation for this proposal. This study is taking advantage of new technological developments in high-speed volumetric imaging and will allow for quantitative functional analysis of the natural fertilization process and fertilization failures in mouse models of human infertility. This project will provide new insight into the process of mammalian fertilization in its native state and lead to a better understanding of pathologies resulting in infertility. Mouse models provide an irreplaceable resource for healthcare, with thousands of genetic and epigenetic preclinical models available to study human diseases and an established pipeline for translating the knowledge from mouse models into clinical practice. This study will also enable the global international effort to inform human reproductive healthcare strategies through functional phenotyping of hundreds of mouse models linked to infertility.