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Wittmann, A. ; Grimm, M.* ; Scherthan, H.* ; Horsch, M. ; Beckers, J. ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Ford, S.J. ; Burton, N.C. ; Razansky, D. ; Trümbach, D. ; Aichler, M. ; Walch, A.K. ; Calzada-Wack, J. ; Neff, F. ; Wurst, W. ; Hartmann, T.* ; Floß, T.

Sphingomyelin synthase 1 is essential for male fertility in mice.

PLoS ONE 11:e0164298 (2016)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Polyunsaturated Fatty-acids; Double-strand Breaks; Long-chain; Germ-cells; Mammalian Spermatogenesis; Chromosome Inactivation; Lysine-9 Methylation; Mass-spectrometry; Deficient Mice; Sertoli-cells
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 11, Heft: 10, Seiten: , Artikelnummer: e0164298 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
Institute of Biological and Medical Imaging (IBMI)
Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)
POF Topic(s) 30204 - Cell Programming and Repair
30201 - Metabolic Health
30205 - Bioengineering and Digital Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-500500-001
G-500600-001
G-500600-004
G-500692-001
G-505590-001
G-500300-001
G-500390-001
PubMed ID 27788151
DOI 10.1371/journal.pone.0164298
WOS ID WOS:000389604900016
Scopus ID 84992738264
Erfassungsdatum 2016-10-28
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