Biology subjects

Pepi, L. E.

Publications and source records attributed to Pepi, L. E..

3 recordsLinked to original sources

bioRxiv2023

Siglecs in the Porcine Oviduct and Sialylated Ligands on Sperm: Roles in the Formation of the Sperm Reservoir

AbstractDuring mammalian insemination, most of the deposited sperm are lost by retrograde flow or the female reproductive tracts immune response. Once semen enters the uterus, seminal fluid and sperm elicit leukocyte infiltration that contributes to the elimination of sperm in the uterus. However, unlike the uterus, invading sperm do not trigger a phagocytic response in the oviduct in the absence of dysfunction or disease states. Thus, the oviduct possesses a distinct immunological microenvironment that tolerates sperm while maintaining the capacity to respond to pathogens. It has been suggested that sperm glycocalyx contributes to innate oviductal tolerance, but the cell and molecular mechanisms are not understood. The current investigation focused on the role of sialic acid-containing glycoconjugates on sperm and their potential to elicit innate tolerance via cognate sialic acid-binding immunoglobulin-type lectins (Siglecs) expressed in the oviduct. In this manuscript, we report our discovery of eight Siglecs (Siglecs-1, -2, -3, -5, -10, -11, -14, -15) expressed in the lower pig oviduct, five of which are known for immune inhibitory functions (Siglecs-2, -3, -5, -10, and -11) and how these may play a role in achieving sperm-induced immune suppression in the oviduct microenvironment. Mass spectrometry profiling of porcine sperm revealed the presence of a mixture of 2,3 and 2,6 linked sialic acids with 2,3-linked sialic acids as the dominant linkage. Of the detected glycans, several sialic acid-containing glycoconjugates were identified as potential ligands for Siglecs (among O-linked glycans: NeuAc1GalNAc1, NeuGc1GalNAc1, NeuAc2Gal1GalNAc1; attached to glycolipids: NeuAc2Gal1GalNAc1Gal1Glc1, Fuc1Gal1GalNAc1NeuAc1Gal1Glc1). This is the first report of Siglec expression in the mammalian oviduct and total glycan analysis of porcine sperm. The results of this study reveal the potential for a sperm-sialoglycan and oviductal-Siglec axis that may contribute to the distinct immunophysiology of the oviduct fundamentally required for undisrupted reproduction in mammals.

biochemistry↗

bioRxiv2022

Comparative Mucomic Analysis of Three Functionally Distinct Cornu aspersum Secretions

Every animal secretes mucus, placing them among the most diverse biological materials. Mucus hydrogels are complex mixtures of water, ions, carbohydrates, and proteins. Uncertainty surrounding their composition and how interactions between components contribute to mucus function complicates efforts to exploit their properties. There is substantial interest in commercializing mucus from the garden snail, Cornu aspersum, for skincare, drug delivery, tissue engineering, and composite materials. C. asperum secretes three mucus -- one shielding the animal from environmental threats, one adhesive mucus from the pedal surface of the foot, and another pedal mucus that is lubricating. It remains a mystery how compositional differences account for their substantially different properties. Here, we characterize mucus proteins, glycosylation, ion content, and mechanical properties to understand structure-function relationships through an integrative "mucomics" approach. We identify new macromolecular components of these hydrogels, including a novel protein class termed Conserved Anterior Mollusk Proteins (CAMPs). Revealing differences between C. aspersum mucus shows how considering structure at all levels can inform the design of mucus-inspired materials.

biochemistry↗

bioRxiv2021

Metabolic heritage mapping: heterogenous pools of cytoplasmic nucleotide sugars are selectively utilized by various glycosyltransferases

Biosynthesis of macromolecules requires precursors such as sugars or amino acids, originating from exogenous/dietary sources, reutilization/salvage of degraded molecules or de novo synthesis. Since these sources are assumed to contribute to one homogenous pool, their individual contributions are often overlooked. Protein glycosylation uses monosaccharides from all the above sources to produce nucleotide sugars required to assemble hundreds of distinct glycans. Here we demonstrate that cells identify the origin/heritage of the monosaccharide, fucose, for glycosylation. We measured the contribution of GDP-fucose from each of these sources for glycan synthesis and found that different fucosyltransferases, individual glycoproteins, and linkage-specific fucose residues identify and select different GDP-fucose pools dependent on their heritage. This supports the hypothesis that GDP-fucose exists in multiple, distinct pools, not as a single homogenous pool. The selection is tightly regulated since the overall pool size remains constant. We present novel perspectives on monosaccharide metabolism, which may have general applicability.

biochemistry↗