Preprint links disrupted glycosylation and deglycosylation to impaired sperm function in zebrafish

A preprint on bioRxiv reports findings from a zebrafish (Danio rerio) study examining how deficiencies in glycosylation and deglycosylation — the enzymatic processes that attach and remove oligosaccharide chains from proteins — affect sperm biology. The work is motivated by congenital disorders of glycosylation (CDGs) and congenital disorders of deglycosylation (CDDGs), rare and often serious human conditions in which loss-of-function variants disrupt these enzymatic pathways.

The authors' proposed mechanism centres on the downstream consequences of failed oligosaccharide processing: abnormal protein folding leads to protein aggregates, which in turn generate reactive oxygen species (ROS). Because sperm cells contain unusually high concentrations of polyunsaturated fatty acids and are therefore especially sensitive to oxidative stress, the authors suggest that CDG- and CDDG-related enzyme deficiencies may impair sperm condition through this pathway, contributing to male infertility.

Zebrafish were used as a model because sperm development in Danio rerio shares molecular features with mammalian spermatogenesis while offering experimental tractability. The preprint has not yet been peer-reviewed. Researchers working on CDGs, reproductive genetics, or zebrafish biology will find the mechanistic framing of interest, and the findings may inform future understanding of fertility in individuals with these rare conditions.