Project Summary/Abstract Siglecs in the Porcine Oviduct: Roles in the Formation of the Sperm Reservoir and Sperm Immune Response In mammals, only a small fraction of the deposited spermatozoa in the female reproductive tract reach the oviduct. Once in the oviduct, sperm bind to the oviductal epithelium, forming the functional sperm reservoir, which is crucial in prolonging sperm lifespan by inducing sperm into a quiescent state and providing these foreign gametes with an immune-suppressed environment. Siglecs are immunomodulatory receptors that recognize sialic acid-containing glycoconjugates. Using the pig as a model, we have discovered the presence of up to eight different Siglecs in the porcine oviduct, five of which are immune inhibitory. We have also characterized the N- and O-glycans and glycolipids present in porcine spermatozoa. Our results have identified the presence of several sialic acid-containing glycoconjugates on porcine sperm that are ligands for Siglecs. We hypothesize that the interactions of sialylated glycans of sperm with Siglecs from the oviduct are essential for sperm adhesion to the epithelium and sperm survival by suppressing leukocyte infiltration and the local innate immune response. The overall goal of this study is to develop a clear understanding of the role of Siglecs in the oviduct and sperm sialic acids during the formation of the sperm reservoir. The Specific Aims are 1) to determine the cellular location and abundance of Siglecs in the oviduct epithelium and sialic acid terminating glycans on sperm, 2) to determine the role of Siglec-1 and other Siglecs in sperm adhesion to oviduct cells, and 3) to determine the role of oviduct Siglecs in local immune regulation upon sperm-oviduct interactions. To address these aims I will utilize a combination of biochemical, cell and molecular, biological, and genomic approaches along with both in-vitro and in-vivo models. The findings from this study have practical applications such as enhanced diagnosis of idiopathic infertility and the development of novel approaches to regulating fertility such as the discovery of new contraceptive targets. This research training plan will provide me with training in a variety of cutting-edge and foundational techniques using an interdisciplinary approach that includes reproduction, immunology, and glycobiology. Moreover, it will support opportunities for career development to prepare me for a successful career in science. The outstanding scientific environment of the University of Illinois will provide me with multiple learning opportunities and the resources to accomplish this study. Dr. Miller, with proven mentoring experience and expertise in the study of the sperm-oviduct interaction, as well as my co-sponsors Dr. McKim and Dr. Nowak, will guide me in the success of the proposed research training plan and my scientific career development.

Project Narrative Cells lining the lower part of the oviduct retain sperm to form a reservoir before fertilization. The goal of this study is to define how complex sugars on the sperm surface and newly-discovered Siglec proteins in the reservoir surface contribute to sperm adhesion and regulation of the local immune system. The long-term outcome of our findings could result in the development of novel contraceptive targets and help us understand some of the causes of idiopathic infertility.