Diminution in sperm quantity and quality in mouse models of Duchenne Muscular Dystrophy induced by a myostatin-based muscle growth-promoting intervention


Submitted: 19 February 2020
Accepted: 12 March 2020
Published: 22 June 2020
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Authors

  • Danielle Vaughan School of Biological Sciences, University of Reading, United Kingdom.
  • Oliver Kretz III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Ali Alqallaf School of Biological Sciences, University of Reading, United Kingdom.
  • Robert Mitchell School of Biological Sciences, University of Reading, United Kingdom.
  • Jennie L. von der Heide III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Sakthivel Vaiyapuri School of Pharmacy, University of Reading, United Kingdom.
  • Antonios Matsakas Molecular Physiology Laboratory, Centre for Atherothrombosis & Metabolic Disease, Hull York Medical School, Hull, United Kingdom.
  • Arja Pasternack Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
  • Henry Collins-Hooper School of Biological Sciences, University of Reading, United Kingdom.
  • Olli Ritvos Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
  • Randy Ballesteros Royal Veterinary College, London, United Kingdom.
  • Tobias B. Huber III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Helge Amthor Versailles Saint-Quentin-en-Yvelines University, INSERM U1179, LIA BAHN CSM, Montigny-le-Bretonneux, France.
  • Abir Mukherjee Royal Veterinary College, London, United Kingdom.
  • Ketan Patel School of Biological Sciences, University of Reading, United Kingdom.

Duchenne Muscular Dystrophy is a devastating disease caused by the absence of a functional rod-shaped cytoplasmic protein called dystrophin. Several avenues are being developed aimed to restore dystrophin expression in boys affected by this X-linked disease. However, its complete cure is likely to need combinational approaches which may include regimes aimed at restoring muscle mass. Augmenting muscle growth through the manipulation of the Myostatin/Activin signalling axis has received much attention. However, we have recently shown that while manipulation of this axis in wild type mice using the sActRIIB ligand trap indeed results in muscle growth, it also had a detrimental impact on the testis. Here we examined the impact of administering a powerful Myostatin/Activin antagonist in two mouse models of Duchenne Muscular Dystrophy. We report that whilst the impact on muscle growth was not always positive, both models showed attenuated testis development. Sperm number, motility and ultrastructure were significantly affected by the sActRIIB treatment. Our report suggests that interventions based on Myostatin/Activin should investigate off-target effects on tissues as well as muscle.


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Vaughan, D., Kretz, O., Alqallaf, A., Mitchell, R., von der Heide, J. L., Vaiyapuri, S., Matsakas, A., Pasternack, A., Collins-Hooper, H., Ritvos, O., Ballesteros, R., Huber, T. B., Amthor, H., Mukherjee, A., & Patel, K. (2020). Diminution in sperm quantity and quality in mouse models of Duchenne Muscular Dystrophy induced by a myostatin-based muscle growth-promoting intervention. European Journal of Translational Myology, 30(2), 276–285. https://doi.org/10.4081/ejtm.2020.8904

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