(137) The Role of Siglecs in Selective Sperm Clearance within the Porcine Oviduct.

Abstract Authors: Hao-Chun Fan1, Leonardo Molina1, David J. Miller1, Adrienne M. Antonson1. 
1Department of Animal Sciences, University of Illinois at Urbana Champaign, Urbana, IL.

Abstract Text: During mammalian fertilization, most of the sperm that invade the uterus triggers leukocyte infiltration and is subsequently cleared. In contrast, sperm in the oviduct does not trigger this phagocytic response. Nonetheless, the oviduct maintains its capacity to respond to pathogens. The formation of this unique immune environment in the oviduct is not fully understood but might be related to the glycocalyx on the sperm surface. Notably, the sialic acid on the glycocalyx of the sperm surface and the sialic acid-binding immunoglobulin-like lectins (Siglecs) on the epithelial cells of the female reproductive tract have been shown to influence the clearance of sperm in the uterus. Our preliminary research has also identified the presence of numerous inhibitory Siglecs (Siglecs-2, -3, -5, -10, and -11) in the epithelial cells of the oviduct. Based on these findings, we hypothesize that when sperm attaches to the uterine epithelium, the sialic acid on their surface interacts with immune-activating Siglecs on epithelial cells. This interaction triggers downstream signaling, leading to the production of cytokines and chemokines that activate and attract peripheral blood mononuclear cells (PBMCs) to clear the sperm. In contrast, in the oviduct, sperm may activate immune-inhibiting receptors, reducing the production of PBMC-activating factors. To test this hypothesis, we aim to establish a primary epithelial cell culture model of the oviduct and uterus using an air-liquid interface cell culture system. By adding PBMCs to the liquid side, we can observe the response of PBMCs to epithelial cell stimulation in this co-culture model. Additionally, by treating sperm with different enzymes, such as neuraminidase or sialyltransferases, and adding them to the air side, we can determine whether the PBMC response is mediated by the involvement of Siglecs on the epithelial cells. This study might provide new insights into the mechanisms underlying selective sperm clearance and the immune privilege of the oviduct, potentially uncovering novel therapeutic targets for reproductive health.