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.
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Authors | 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 |
Journal | PloS one
(PLoS One)
Vol. 11
Issue 10
Pg. e0164298
( 2016)
ISSN: 1932-6203 [Electronic] United States |
PMID | 27788151
(Publication Type: Journal Article)
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Chemical References |
- Fatty Acids, Omega-3
- Sgms1 protein, mouse
- Transferases (Other Substituted Phosphate Groups)
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Topics |
- Aging
(physiology)
- Alternative Splicing
- Animals
- Epididymis
(drug effects, metabolism)
- Fatty Acids, Omega-3
(biosynthesis, pharmacology)
- Fertility
(drug effects)
- Infertility, Male
(enzymology)
- Lipid Metabolism
(drug effects)
- Male
- Mice
- Mutagenesis, Insertional
- Promoter Regions, Genetic
(genetics)
- Spermatogenesis
(drug effects)
- Testis
(drug effects, metabolism)
- Transferases (Other Substituted Phosphate Groups)
(genetics, metabolism)
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