| Description |
Creation of the next generation by sexual reproduction requires the fusion of male and female gametes. For many species, this entails a sessile oocyte and a highly motile spermatozoon with remarkable ability to sense and migrate through the often structurally and chemically complex reproductive tract of a female. Despite many years of research, our understanding of the basic components of male-factor infertility, in any species, is poor. While we know of many factors involved or associated with sperm success, few have been well characterized at the molecular level. Understanding how sperm successfully accomplish their journey is critical to human health and the health of ecosystems that hinge on the reproductive success and balance of species within. The study of reproductive biology is challenging partially due to the lack of direct conservation in many genes involved in the process of reproduction. Therefore, it is critical to investigate reproduction in a wide variety of species both to identify conserved themes and also to discover novel cell biological processes. In this dissertation, I study the secreted serine protease inhibitor SWM-1, a protein known for its critical role in male fertility of the nematode Caenorhabditis elegans. Through this work, I have discovered that SWM-1 is produced in an unlikely source of somatic cells: body wall muscle. From muscle, SWM-1 is secreted into the body fluid of the worm and enters the gonad to perform its critical role of preventing sperm from premature motility, which causes male infertility. I show that there is bi-directional movement of proteins between the body fluid and gonadal structures, which may be a widespread phenomenon. Through this work, I also discovered that SWM-1 is a seminal fluid protein and a component of the sperm migratory environment though its role in this environment remains unknown. I expand on our knowledge of the molecular relationship to SWM-1's likely target, the protease TRY-5, by probing its protease inhibitory domains and visualizing SWM-1 and TRY-5 in combination. Lastly, I began initial characterization of other mutants that affect the acquisition of motility. This work adds to the knowledge of the role of proteolysis regulators in male reproductive success and the regulation of cell motility. Moreover, my finding that muscle is a source of SWM-1 and that SWM-1 is also a seminal fluid protein reveals a novel means of ensuring sperm success and highlights the utility of C. elegans as a system to study secretory and reproductive biology. |
