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

doi:10.1371/journal.pone.0164298

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

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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 language	English
Article number	e0164298
Journal	PLoS ONE
Volume	11
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0164298
State	Published - Oct 2016

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Wittmann, A., Grimm, M. O. W., Scherthan, H., Horsch, M., Beckers, J., Fuchs, H., Gailus-Durner, V., De Angelis, M. H., 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. (2016). Sphingomyelin synthase 1 is essential for male fertility in mice. PLoS ONE, 11(10), Article e0164298. https://doi.org/10.1371/journal.pone.0164298

@article{eae8b7871feb489faeea90319dea2c02,

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.",

author = "Anke Wittmann and Grimm, {Marcus O.W.} and Harry Scherthan and Marion Horsch and Johannes Beckers and Helmut Fuchs and Valerie Gailus-Durner and {De Angelis}, {Martin Hrab{\v e}} and Ford, {Steven J.} and Burton, {Neal C.} and Daniel Razansky and Dietrich Tr{\"u}mbach and Michaela Aichler and Walch, {Axel Karl} and Julia Calzada-Wack and Frauke Neff and Wolfgang Wurst and Tobias Hartmann and Thomas Floss",

note = "Publisher Copyright: Copyright {\textcopyright} 2016 Wittmann et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2016",

month = oct,

doi = "10.1371/journal.pone.0164298",

language = "English",

volume = "11",

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Wittmann, A, Grimm, MOW, Scherthan, H, Horsch, M, Beckers, J, Fuchs, H, Gailus-Durner, V, De Angelis, MH, Ford, SJ, Burton, NC, Razansky, D, Trümbach, D, Aichler, M, Walch, AK, Calzada-Wack, J, Neff, F, Wurst, W, Hartmann, T & Floss, T 2016, 'Sphingomyelin synthase 1 is essential for male fertility in mice', PLoS ONE, vol. 11, no. 10, e0164298. https://doi.org/10.1371/journal.pone.0164298

TY - JOUR

T1 - Sphingomyelin synthase 1 is essential for male fertility in mice

AU - Wittmann, Anke

AU - Grimm, Marcus O.W.

AU - Scherthan, Harry

AU - Horsch, Marion

AU - Beckers, Johannes

AU - Fuchs, Helmut

AU - Gailus-Durner, Valerie

AU - De Angelis, Martin Hrabě

AU - Ford, Steven J.

AU - Burton, Neal C.

AU - Razansky, Daniel

AU - Trümbach, Dietrich

AU - Aichler, Michaela

AU - Walch, Axel Karl

AU - Calzada-Wack, Julia

AU - Neff, Frauke

AU - Wurst, Wolfgang

AU - Hartmann, Tobias

AU - Floss, Thomas

N1 - Publisher Copyright: Copyright © 2016 Wittmann et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2016/10

Y1 - 2016/10

N2 - 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.

AB - 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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U2 - 10.1371/journal.pone.0164298

DO - 10.1371/journal.pone.0164298

M3 - Article

C2 - 27788151

AN - SCOPUS:84992738264

SN - 1932-6203

VL - 11

JO - PLoS ONE

JF - PLoS ONE

IS - 10

M1 - e0164298

ER -

Sphingomyelin synthase 1 is essential for male fertility in mice

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