Hoch ungesättigte Sphingolipide: Biosynthese Expression und biologische Funktion während der Spermatogenese

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In contrast to cholesterol and phospholipids including sphingomyelin, glycosphingolipids (GSLs) are cell type and differentiation stage specifically expressed in mammalian cells and contain almost exclusively saturated fatty acid residues. Not only the sugar head groups of GSLs but also their membrane anchors, i.e. the ceramide moieties including the N-linked fatty acyl chain show a cell type specific pattern (Kolter and Sandhoff, 1999). In our previous work we discovered in mouse testis, structurally characterized and to some extent histologically localized, a novel class of GSLs (8 members in mice). They were defined as a novel class because these fucosylated GSLs (FGSLs) contain almost exclusively polyunsaturated (polyenoic, 4-6 double bonds) very long chain (C28-C32) fatty acyl (VLCFA) residues (Sandhoff et al., 2005). Mice lacking ganglio-series GSLs are also deficient in this novel type of testicular polyenoic FGSLs. Spermatogenesis of such mice is arrested at the stage of immature round spermatids with the consequence of male infertility (Takamiya et al., 1998). The aim of this project is to understand the biosynthesis, localization and biological function of this novel class of polyunsaturated sphingolipids. Besides expanding the basic knowledge in this field, the expected results of this project may help to gain deeper insight into the possible causes of male infertility. They may, in addition, open new fields for male contraception.