Novel class of glycosphingolipids involved in male fertility.
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.
Sandhoff
Roger
R
Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany. rsandhoff@dkfz-heidelberg.de
Geyer
Rudolf
R
Jennemann
Richard
R
Paret
Claudia
C
Kiss
Eva
E
Yamashita
Tadashi
T
Gorgas
Karin
K
Sijmonsma
Tjeerd P
TP
Iwamori
Masao
M
Finaz
Catherine
C
Proia
Richard L
RL
Wiegandt
Herbert
H
Gröne
Hermann-Josef
HJ
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
D005231:Fatty Acids, Unsaturated; D006028:Glycosphingolipids; D005643:Fucose; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase; D012799:Sialyltransferases; C021343:haematoside synthetase