Sphingomyelin synthase 1 is essential for male fertility in mice

Anke Wittmann, Marcus O.W. Grimm, Harry Scherthan, Marion Horsch, Johannes Beckers, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabě De Angelis, Steven J. Ford, Neal C. Burton, Daniel Razansky, Dietrich Trümbach, Michaela Aichler, Axel Karl Walch, Julia Calzada-Wack, Frauke Neff, Wolfgang Wurst, Tobias Hartmann, Thomas Floss

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish
Article numbere0164298
JournalPLoS ONE
Volume11
Issue number10
DOIs
StatePublished - Oct 2016

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