1 research outputs found
Male Germ Cells Require Polyenoic Sphingolipids with Complex Glycosylation for Completion of Meiosis: A LINK TO CERAMIDE SYNTHASE-3*S⃞
Previously, it was found that a novel class of neutral fucosylated
glycosphingolipids (GSLs) is required for male fertility. These lipids contain
very long-chain (C26-C32) polyunsaturated (4-6 double bonds) fatty acid
residues (VLC-PUFAs). To assess the role of these complex GSLs in
spermatogenesis, we have now investigated with which of the testicular cell
types these lipids are associated. During postnatal development, complex
glycosylated and simple VLC-PUFA sphingolipids were first detectable at day
15, when the most advanced germ cells are pachytene spermatocytes. Their
synthesis is most likely driven by ceramide synthase-3. This enzyme is encoded
by the Cers3/Lass3 gene (longevity assurance genes), and out
of six members of this gene family, only Cers3 mRNA expression was
limited to germ cells, where it was up-regulated more than 700-fold during
postnatal testicular maturation. Increasing levels of neutral complex VLC-PUFA
GSLs also correlated with the progression of spermatogenesis in a series of
male sterile mutants with arrests at different stages of spermatogenesis.
Remarkably, fucosylation of the complex VLC-PUFA GSLs was not essential for
spermatogenesis, as fucosylation-deficient mice produced nonfucosylated
versions of the complex testicular VLC-PUFA GSLs, had complete
spermatogenesis, and were fertile. Nevertheless, sterile
Galgt1-/- mice, with a defective meiotic cytokinesis and a
subsequent block in spermiogenesis, lacked complex but contained simple
VLC-PUFA GSLs, as well as VLC-PUFA ceramides and sphingomyelins, indicating
that the latter lipids are not sufficient for completion of spermatogenesis.
Thus, our data imply that both glycans and the particular acyl chains of
germinal sphingolipids are relevant for proper completion of meiosis