The female reproductive tract contains multiple innate sialic acid-binding immunoglobulin-like lectins (Siglecs) that facilitate sperm survival

A sperm that fertilizes an egg has successfully survived multiple checkpoints within the female reproductive tract, termed pre-fertilization events. The leukocytic response is a pre-fertilization event in which sperm trigger an immune response that promotes homing of circulating leukocytes to the uterine lumen to destroy most sperm. Various glycoconjugates decorate the sperm surface, including sialic acids, which are abundant at the sperm surface where they cap most glycan chains and regulate sperm migration through cervical mucus, formation of the sperm oviductal reservoir, and sperm capacitation. However, the role of sperm-associated sialic acids in the leukocytic reaction remains unknown. The cognate endogenous binding partners of sialic acids, sialic acid-binding immunoglobulin-like lectins (Siglecs) play a pivotal role in regulating many immune responses. Here we investigated whether sperm-associated sialic acids inhibit activation of neutrophils, one of the major immune cells involved in the leukocytic reaction. We used in vitro interactions between sperm and neutrophils as well as binding assays between sperm and recombinant Siglec-Fc chimeric proteins to measure interactions. Moreover, we examined whether Siglecs are expressed on human and mouse endometria, which have a role in initiating the leukocytic reaction. Surprisingly less sialylated, capacitated, sperm did not increase neutrophil activation in vitro. However, we observed expression of several Siglecs on the endometrium and that these receptors interact with sialylated sperm. Our results indicate that sperm sialic acids may interact with endometrial Siglecs and that these interactions facilitate sperm survival in the face of female immunity.