Epididymal St3gal2-mediated α2,3-sialylation regulates murine sperm motility and correlates with N-glycan alterations in human asthenozoospermia.

Authors

Yujia Zhai, Yueyue Li, Yuping Zhang, Ruohan Wang, Yilun Wu, Ying Feng, Haojie Lu, Fang Ma

Published in

International journal of biological macromolecules. Pages 154667. Sep 28, 2026. Epub Sep 28, 2026.

Abstract

Sialic acid residues on the sperm surface play crucial roles in sperm maturation, capacitation, and sperm-oocyte interactions. Here, we investigated the dynamic regulation of α2,3-sialylation on the sperm membrane during epididymal maturation in mice, with a focus on the sialyltransferase St3gal2. St3gal2 is highly expressed in the caput epididymis and mediates the progressive accumulation of α2,3-linked sialic acid on the murine sperm surface during epididymal transit. Enzymatic removal of surface α2,3-sialic acid significantly reduced mouse sperm progressive motility, whereas co-incubation of desialylated mouse sperm with conditioned medium from St3gal2-overexpressing COS-7 cells restored both surface α2,3-sialylation and motility, establishing a direct functional link between St3gal2 activity and sperm movement. To extend these findings to human reproductive pathology, we performed systematic N-glycomic profiling of sperm membrane proteins from healthy donors (PR ≥ 32%, n = 18) and asthenozoospermic donors (PR < 32%, n = 15) by MALDI-MS. α2,3-Sialylated N-glycans were positively correlated with progressive motility and significantly reduced in asthenozoospermic sperm, while fucosylated N-glycans were significantly elevated in asthenozoospermia. α2,6-Sialylated N-glycans showed no significant difference between groups and no significant association with progressive motility. Lectin-based flow cytometry independently confirmed increased surface fucosylation and decreased surface α2,3-sialylation in asthenozoospermic sperm. Together, these findings establish a causal role for St3gal2-mediated α2,3-sialylation in murine sperm motility and reveal a characteristic N-glycan imbalance - reduced α2,3-sialylation and elevated fucosylation - associated with human asthenozoospermia, identifying the sperm surface glycocalyx as a potential target for therapeutic intervention in motility-related male infertility.

PMID:
42805527
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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