Male Germ Cells Require Polyenoic Sphingolipids with Complex Glycosylation for Completion of Meiosis
By M. Rabionet, A. C. van der Spoel, Chia-Chen Chuang, Benita von Tümpling-Radosta, M. Litjens, D. Bouwmeester, Christina C. Hellbusch, C. Körner, H. Wiegandt, K. Gorgas and 3 more. 2008
114 citations recorded by the source corpus.
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.
Subfields: Physiology, Public Health, Environmental and Occupational Health, Reproductive Medicine
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Citations in the corpus
- Mammalian Ceramide Synthases (2010, background): “Indeed, the increase in levels of glycosphingolipids containing very long chain (C26–C32) polyunsaturated fatty acid (LCPUFA), which are essential for spermatogenesis, coincides with a strong elevation of CerS3 mRNA (63).”
- Potentiation of cannabinoid-induced cytotoxicity in Mantle Cell Lymphoma through modulation of ceramide metabolism (2009, background): “CerS3 is regarded as a minor CerS that has mainly been described in skin and testis (10, 39) and has been shown to synthesize the longer ceramide”