title: Arylsulfatase A deficiency causes seminolipid accumulation and a lysosomal storage disorder in Sertoli cells.
abstract: Sulfogalactosylglycerolipid (SGG) is the major sulfoglycolipid of male germ cells. During spermatogenesis, apoptosis occurs in >50% of total germ cells. Sertoli cells phagocytose these apoptotic germ cells and degrade their components using lysosomal enzymes. Here we demonstrated that SGG was a physiological substrate of Sertoli lysosomal arylsulfatase A (ARSA). SGG accumulated in Sertoli cells of Arsa(-/-) mice, and at 8 months of age, this buildup led to lysosomal swelling and other cellular abnormalities typical of a lysosomal storage disorder. This disorder likely compromised Sertoli cell functions, manifesting as impaired spermatogenesis and production of sperm with near-zero fertilizing ability in vitro. Fecundity of Arsa(-/-) males was thus reduced when they were older than 5 months. Sperm SGG is known for its roles in fertilization. Therefore, the minimal sperm fertilizing ability of 8-month-old Arsa(-/-) males may be explained by the 50% reduction of their sperm SGG levels, a result that was also observed in testicular germ cells. These unexpected decreases in SGG levels might be partly due to depletion of the backbone lipid palmitylpalmitoylglycerol that is generated from the SGG degradation pathway in Sertoli cells and normally recycled to new generations of primary spermatocytes for SGG synthesis.
authors.affiliation: Chronic Diseases Program, Ottawa Hospital Research Institute, Ottawa, ON K1Y4E9, Canada; Department of Biochemistry/Microbiology/Immunology University of Ottawa, Ottawa ON K1H8M5, Canada.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Xu
authors.affiliation: Chronic Diseases Program, Ottawa Hospital Research Institute, Ottawa, ON K1Y4E9, Canada; Department of Biochemistry/Microbiology/Immunology University of Ottawa, Ottawa ON K1H8M5, Canada.
authors.forename: Kessiri
authors.initials: K
authors.lastname: Kongmanas
authors.affiliation: Chronic Diseases Program, Ottawa Hospital Research Institute, Ottawa, ON K1Y4E9, Canada; Department of Biochemistry/Microbiology/Immunology University of Ottawa, Ottawa ON K1H8M5, Canada; Department of Obstetrics/Gynaecology, Faculty of Medicine, University of Ottawa, Ottawa ON K1H8M5, Canada.
authors.forename: Suraj
authors.initials: S
authors.lastname: Kadunganattil
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A2B2, Canada.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: Departments of Pediatrics University of Western Ontario, London, ON N6A5W9, Canada; Biochemistry, University of Western Ontario, London, ON N6A5W9, Canada.
authors.forename: Tony
authors.initials: T
authors.lastname: Rupar
authors.affiliation: Department of Molecular Anatomy, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan; and.
authors.forename: Naoko
authors.initials: N
authors.lastname: Goto-Inoue
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A2B2, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Hermo
authors.affiliation: Pasarow Mass Spectrometry Laboratory, NPI-Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90024.
authors.forename: Kym F
authors.initials: KF
authors.lastname: Faull
authors.affiliation: Chronic Diseases Program, Ottawa Hospital Research Institute, Ottawa, ON K1Y4E9, Canada; Department of Biochemistry/Microbiology/Immunology University of Ottawa, Ottawa ON K1H8M5, Canada; Department of Obstetrics/Gynaecology, Faculty of Medicine, University of Ottawa, Ottawa ON K1H8M5, Canada. Electronic address: ntanphaichitr@ohri.ca.
authors.forename: Nongnuj
authors.initials: N
authors.lastname: Tanphaichitr
mesh_terms: D000818:Animals; D002553:Cerebroside-Sulfatase / Q000172:deficiency* / Q000378:metabolism; D005298:Fertility; D038983:Galactolipids / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism*; D016464:Lysosomal Storage Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012708:Sertoli Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D013091:Spermatogenesis
chemical_list: D038983:Galactolipids; D006017:Glycolipids; C009233:seminolipid; C414346:sulfogalactosylglycerolipid; D002553:Cerebroside-Sulfatase