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

Vaughan, Danielle; Kretz, Oliver; Alqallaf, Ali; Mitchell, Robert; von der Heide, Jenny; Vaiyapuri, Sakthivel; Matsakas, Antonios; Pasternack, Arja; Collins-Hooper, Henry; Ritvos, Olli; Ballesteros, Randy; Huber, Tobias B.; Amthor, Helge; Mukherjee, Abir; Patel, Ketan

Authors

Danielle Vaughan

Oliver Kretz

Ali Alqallaf

Robert Mitchell

Jenny von der Heide

Sakthivel Vaiyapuri

Antonios Matsakas

Arja Pasternack

Henry Collins-Hooper

Olli Ritvos

Randy Ballesteros

Tobias B. Huber

Helge Amthor

Abir Mukherjee

Ketan Patel



Contributors

Antonios Matsakas
Data Collector

Abstract

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.

Journal Article Type Article
Journal European Journal of Translational Myology
Print ISSN 2037-7452
Publisher PAGEpress
Peer Reviewed Peer Reviewed
Volume 30
Issue 2
Pages 276-285
APA6 Citation Vaughan, D., Kretz, O., Alqallaf, A., Mitchell, R., von der Heide, J., Vaiyapuri, S., …Patel, K. (in press). 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.0.8904
DOI https://doi.org/10.4081/ejtm.0.8904
Keywords Duchenne Muscular Dystrophy; Mdx; Muscle hypertrophy; Testis; Activin; Myostatin
Publisher URL https://www.pagepressjournals.org/index.php/bam/article/view/8904

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