ArticlePloS one2026
Alpha-N-acetylglucosaminidase (NAGLU) inactivation causes morphological damage to the ultrastructural appearance of epididymal mononuclear phagocytes (eMPs) and epithelial cells of the epididymis in adult mice.
Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Heparan sulfate (HS) a glycosaminoglycan family of carbohydrates, is covalently attached to core proteins forming heparan sulfate proteoglycans (HSPGs) which are found on the surface of cells. Following endocytosis, HSPGs are degraded within lysosomes by several enzymes, including α-N-acetylglucosaminidase (NAGLU). Absence of NAGLU leads to Mucopolysaccharidosis III type B (Sanfilippo type B), a lysosomal storage disease, which in Naglu-/- mice was suggested to result in infertility. Since endocytosis is a feature of epididymal epithelial and immune cells, a plausible explanation could be excessive accumulation of lysosomes in these cells in 7-month-old mice. EM analysis revealed a massive accumulation of pale lysosomes (LM-IHC/LAMP2 + /cathepsin B+) of varying shapes and sizes in the cytoplasm of principal cells, unlike the small dense spherical lysosomes of wild type mice. Their presence had a profound effect on the integrity of organelles such as the ER, Golgi, mitochondria and nucleus. In addition, the epithelium demonstrated sporadic large, highly vacuolated cells, identified as CD68+ and MOMA+ epididymal mononuclear phagocytes (eMPs), with a cytoplasm dominated by pale lysosomes, some of gigantic size. The plethora of lysosomes overwhelming the cytoplasm suggested an ongoing phagocytic activity to protect the epithelium despite the excessive disruption of their organelles. A distinguishing feature of the content of lysosomes of eMPs was the presence of aggregates of small flattened membranous discs aligned parallel to one another, referred to as zebra bodies. The latter had the appearance of mitochondrial cristae of principal cells and were reactive for a mitochondrial marker, suggesting a phagocytic activity for eMPs of degenerating principal cells. Taken together, our data demonstrates that the accumulation of lysosomes of epithelial cells and eMPs dramatically altered their structural appearance in the absence of NAGLU inducing an inactivation of their critical role in supporting a proper epithelial environment for sperm protection and maturation.
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