title: Novel class of glycosphingolipids involved in male fertility.
abstract: Mice require testicular glycosphingolipids (GSLs) for proper spermatogenesis. Mutant mice strains deficient in specific genes encoding biosynthetic enzymes of the GSL pathway including Galgt1 (encoding GM2 synthase) and Siat9 (encoding GM3 synthase) have been established lacking various overlapping subsets of GSLs. Although male Galgt1-/- mice are infertile, male Siat9-/- mice are fertile. Interestingly, GSLs thought to be essential for male spermatogenesis are not synthesized in either of these mice strains. Hence, these GSLs cannot account for the different phenotypes. A novel class of GSLs was observed composed of eight fucosylated molecules present in fertile but not in infertile mutant mice. These GSLs contain polyunsaturated very long chain fatty acid residues in their ceramide moieties. GSLs of this class are expressed differentially in testicular germ cells. More importantly, the neutral subset of this new GSL class strictly correlates with male fertility. These data implicate polyunsaturated, fucosylated GSLs as essential for spermatogenesis and male mouse fertility.
authors.affiliation: Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany. rsandhoff@dkfz-heidelberg.de
authors.forename: Roger
authors.initials: R
authors.lastname: Sandhoff
authors.forename: Rudolf
authors.initials: R
authors.lastname: Geyer
authors.forename: Richard
authors.initials: R
authors.lastname: Jennemann
authors.forename: Claudia
authors.initials: C
authors.lastname: Paret
authors.forename: Eva
authors.initials: E
authors.lastname: Kiss
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Karin
authors.initials: K
authors.lastname: Gorgas
authors.forename: Tjeerd P
authors.initials: TP
authors.lastname: Sijmonsma
authors.forename: Masao
authors.initials: M
authors.lastname: Iwamori
authors.forename: Catherine
authors.initials: C
authors.lastname: Finaz
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.forename: Herbert
authors.initials: H
authors.lastname: Wiegandt
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
mesh_terms: D000818:Animals; D005231:Fatty Acids, Unsaturated; D005298:Fertility / Q000235:genetics; D005643:Fucose; D006028:Glycosphingolipids / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D012799:Sialyltransferases / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics
chemical_list: D005231:Fatty Acids, Unsaturated; D006028:Glycosphingolipids; D005643:Fucose; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase; D012799:Sialyltransferases; C021343:haematoside synthetase