MAMMALIAN SPERM NAVIGATION WITHIN THE FEMALE REPRODUCTIVE TRACT

Abstract

For successful fertilization in mammals, sperm must migrate through the female reproductive tract, reach the site of fertilization where an egg is released, and fuse with the egg. During this migration within the tract, sperm must use multiple navigational mechanisms to maintain the appropriate swimming behavior as it ascends towards the fertilization site. These navigational mechanisms through which sperm cope with the dynamic conditions within the tract are known to rely upon the biophysical and biochemical clues present in the tract. The central idea of this dissertation is to identify the navigational mechanisms associated with bovine sperm migration using microfluidic devices designed to mimic the biochemical and biophysical properties of the female reproductive tract. We use bovine sperm as our model because the outcomes of this dissertation are intended to be valuable for dairy and beef industries as well as human reproductive medicine. In Chapter 1 and Chapter 2, we focus on two previously known navigational mechanisms: sperm upstream swimming (rheotaxis) and the boundary-following navigation caused by hydrodynamic interactions of sperm with nearby rigid boundaries. We discuss how these two mechanisms are the basis for a motility-based selection of sperm, during which the female reproductive tract selects for the most vigorous ones. In chapter 3, we discuss sperm rolling around its longitudinal axis, and its function in navigation within the female reproductive tract. We demonstrate that sperm rolling is sensitive to ambient fluid viscosity and viscoelasticity. That is, the rheological properties of the swimming media can reversibly suppress rolling and transition sperm swimming behavior from progressive to diffusive circular motion. Since the viscosity and viscoelasticity of the fluid within the female tract vary according to functional region, the tract possibly regulates sperm navigation via modulating the rheological properties of the swimming media and controlling the rolling component. Finally, in Chapter 4, we focus on hyperactivation, as sperm response to biochemical stimuli. We demonstrate that hyperactivation regulates sperm navigation through physical boundaries, which subsequently stimulates a previously unknown mechanism of sperm accumulation in areas with the highest concentration of hyperactivation agonist.