Abstract
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.
Highlights
Are not sufficient for completion of spermatogenesis
In this study we present the following: (i) we classify and localize fucosylated GSLs to different germ cell classes according to their charge; (ii) we demonstrate that polyenoic very long-chain fatty acid-containing sphingolipids in general (FGSLs, GSLs, ceramides, and sphingomyelins) are restricted to germ cells and are expressed in a differentiation stage-specific manner (Fig. 1B); (iii) we link the synthesis of polyenoic VLCFA sphingolipids to the expression of one of six potentialceramide synthases; and (iv) we show the dis
Seminiferous Tubules of KitW-v/KitW Mice Contain Mainly Sertoli Cells and a Residual Number of Spermatogonial Stem Cells—KitW-v/KitW mice lack the receptor c-kit, which is expressed from the differentiating type A spermatogonia through the pachytene spermatocytes
Summary
Are not sufficient for completion of spermatogenesis. our data imply that both glycans and the particular acyl chains of germinal sphingolipids are relevant for proper completion of meiosis. Two features distinguish the polyenoic FGSLs from conventional GSLs as follows: (i) their fucosylation and (ii) their fatty acid tail being mainly of very long chain and polyenoic Both structural features could be essential for proper spermatogenesis, which has still to be clarified. In this study we present the following: (i) we classify and localize fucosylated GSLs to different germ cell classes according to their charge; (ii) we demonstrate that polyenoic very long-chain fatty acid-containing sphingolipids in general (FGSLs, GSLs, ceramides, and sphingomyelins) are restricted to germ cells and are expressed in a differentiation stage-specific manner (Fig. 1B); (iii) we link the synthesis of polyenoic VLCFA sphingolipids to the expression of one of six potential (dihydro)ceramide synthases; and (iv) we show the dis-
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