title: Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice.
abstract: Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility.
authors: Helmholtz Zentrum München, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Anke
authors: A
authors: Wittmann
authors: Saarland University, Experimentelle Neurologie, 66424 Homburg/Saar; Germany.
authors: Marcus O W
authors: MO
authors: Grimm
authors: Institut für Radiobiologie der Bundeswehr in Verb. mit der Univ. Ulm, 80937 Munich, Germany.
authors: Harry
authors: H
authors: Scherthan
authors: Helmholtz Zentrum München, German Mouse Clinic, Institute of Experimental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Marion
authors: M
authors: Horsch
authors: Helmholtz Zentrum München, German Mouse Clinic, Institute of Experimental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.|Technische Universität München, Co Helmholtz-Zentrum München.
authors: Johannes
authors: J
authors: Beckers
authors: Helmholtz Zentrum München, German Mouse Clinic, Institute of Experimental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Helmut
authors: H
authors: Fuchs
authors: Helmholtz Zentrum München, German Mouse Clinic, Institute of Experimental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Valerie
authors: V
authors: Gailus-Durner
authors: Helmholtz Zentrum München, German Mouse Clinic, Institute of Experimental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.|Technische Universität München, Co Helmholtz-Zentrum München.
authors: Martin
authors: M
authors: Hrabě de Angelis
authors: Institute for Biological and Medical Imaging, Helmholtz Zentrum München and Technische Universität München, 85764 Neuherberg, Germany.
authors: Steven J
authors: SJ
authors: Ford
authors: Institute for Biological and Medical Imaging, Helmholtz Zentrum München and Technische Universität München, 85764 Neuherberg, Germany.
authors: Neal C
authors: NC
authors: Burton
authors: Institute for Biological and Medical Imaging, Helmholtz Zentrum München and Technische Universität München, 85764 Neuherberg, Germany.
authors: Daniel
authors: D
authors: Razansky
authors: Helmholtz Zentrum München, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Dietrich
authors: D
authors: Trümbach
authors: Helmholtz Zentrum München, Research Unit Analytical Pathology, Institute of Pathology, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: Michaela
authors: M
authors: Aichler
authors: Helmholtz Zentrum München, Research Unit Analytical Pathology, Institute of Pathology, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: Axel Karl
authors: AK
authors: Walch
authors: Helmholtz Zentrum München, German Mouse Clinic, Institute of Pathology, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Julia
authors: J
authors: Calzada-Wack
authors: Helmholtz Zentrum München, German Mouse Clinic, Institute of Pathology, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Frauke
authors: F
authors: Neff
authors: Helmholtz Zentrum München, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.|Technische Universität München, Co Helmholtz-Zentrum München.|Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE), Site Munich, Schillerstrasse 44, 80336 München, Germany.|Max-Planck-Institute of Psychiatry, Kraepelinstr. 2-10, 80804 München, Germany.
authors: Wolfgang
authors: W
authors: Wurst
authors: Saarland University, Experimentelle Neurologie, 66424 Homburg/Saar; Germany.
authors: Tobias
authors: T
authors: Hartmann
authors: Helmholtz Zentrum München, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.|Technische Universität München, Co Helmholtz-Zentrum München.
authors: Thomas
authors: T
authors: Floss
mesh_terms: D000375:Aging / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis / Q000494:pharmacology; D005298:Fertility / Q000187:drug effects; D007248:Infertility, Male / Q000201:enzymology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D016254:Mutagenesis, Insertional; D011401:Promoter Regions, Genetic / Q000235:genetics; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism*
chemical_list: D015525:Fatty Acids, Omega-3; C556686:Sgms1 protein, mouse; D017855:Transferases (Other Substituted Phosphate Groups)