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Following endocytosis, HSPGs are degraded within lysosomes by several enzymes, including \u03b1-N-acetylglucosaminidase (NAGLU). Absence of NAGLU leads to Mucopolysaccharidosis III type B (Sanfilippo type B), a lysosomal storage disease, which in\n                    <jats:italic>Naglu-\/-<\/jats:italic>\n                    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\u2009+\u2009\/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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0359319","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:47:27Z","timestamp":1790358447000},"page":"e0359319","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.1371","volume":"21","author":[{"given":"Lorena","family":"Carvelli","sequence":"first","affiliation":[{"name":"McGill University","place":["Montreal, Quebec, Canada"],"department":["Department of Anatomy and Cell Biology"]},{"name":"Universidad Nacional de Cuyo","place":["Mendoza, Argentina"],"department":["IHEM-CONICET"]},{"name":"Universidad Nacional de Cuyo","place":["Mendoza, Argentina"],"department":["Facultad de Ciencias Exactas y Naturales"]},{"name":"University of Montreal","place":["Montreal, Quebec, Canada"],"department":["CHU Sainte-Justine Research Centre, Department of Pediatrics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Hermo","sequence":"additional","affiliation":[{"name":"McGill University","place":["Montreal, Quebec, Canada"],"department":["Department of Anatomy and Cell Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Cyr","sequence":"additional","affiliation":[{"name":"Universit\u00e9 du Qu\u00e9bec","place":["Laval, Quebec, Canada"],"department":["INRS-Institut Armand Frappier"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Gregory","sequence":"additional","affiliation":[{"name":"Universit\u00e9 du Qu\u00e9bec","place":["Laval, Quebec, Canada"],"department":["INRS-Institut Armand Frappier"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey V.","family":"Pshezhetsky","sequence":"additional","affiliation":[{"name":"McGill University","place":["Montreal, Quebec, Canada"],"department":["Department of Anatomy and Cell Biology"]},{"name":"University of Montreal","place":["Montreal, Quebec, Canada"],"department":["CHU Sainte-Justine Research Centre, Department of Pediatrics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4882-870X","authenticated-orcid":true,"given":"Carlos R.","family":"Morales","sequence":"additional","affiliation":[{"name":"McGill University","place":["Montreal, Quebec, Canada"],"department":["Department of Anatomy and Cell Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"1","key":"pone.0359319.ref001","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1152\/physrev.1972.52.1.198","article-title":"Kinetics of spermatogenesis in mammals: Seminiferous epithelium cycle and spermatogonial renewal","volume":"52","author":"Y Clermont","year":"1972","journal-title":"Physiol Rev"},{"issue":"33","key":"pone.0359319.ref002","first-page":"25","article-title":"Gametogenesis in the male: Prospects for its control","author":"DW Fawcett","year":"1975","journal-title":"Symp Soc Dev Biol"},{"issue":"1","key":"pone.0359319.ref003","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/biolre\/ioy027","article-title":"50 years of spermatogenesis: Sertoli cells and their interactions with germ cells","volume":"99","author":"MD Griswold","year":"2018","journal-title":"Biol Reprod"},{"issue":"4","key":"pone.0359319.ref004","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/jemt.20786","article-title":"Surfing the wave, cycle, life history, and genes\/proteins expressed by testicular germ cells. 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