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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
Korrespondenzautor
Schlagwörter Polyunsaturated Fatty-acids; Double-strand Breaks; Long-chain; Germ-cells; Mammalian Spermatogenesis; Chromosome Inactivation; Lysine-9 Methylation; Mass-spectrometry; Deficient Mice; Sertoli-cells
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.
Nichtpatentliteratur Publikationen
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)