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Inhibition of Activin/Myostatin signalling impairs mouse testis Inhibition of Activin/Myostatin signalling induces skeletal muscle hypertrophy but impairs mouse testicular development

Matsakas, Antonios; Vaughan, Danielle; Ritvos, Olli; Mitchell, Robert; Kretz, Oliver; Lalowski, Maciej; Amthor, Helge; Chambers, David; Matsakas, Antonios; Pasternack, Arja; Collins-Hooper, Henry; Ballesteros, Randy; Denecke, Bernd; Widera, Darius; Mukherjee, Abir; Patel, Ketan; Huber, Tobias B.

Authors

Antonios Matsakas

Danielle Vaughan

Olli Ritvos

Robert Mitchell

Oliver Kretz

Maciej Lalowski

Helge Amthor

David Chambers

Antonios Matsakas

Arja Pasternack

Henry Collins-Hooper

Randy Ballesteros

Bernd Denecke

Darius Widera

Abir Mukherjee

Ketan Patel

Tobias B. Huber



Abstract

Numerous approaches are being developed to promote post-natal muscle growth based on attenuating Myostatin/Activin signalling for clinical uses such as the treatment neuromuscular diseases, cancer cachexia and sarcopenia. However there have been concerns about the effects of inhibiting Activin on tissues other than skeletal muscle. We intraperitoneally injected mice with the Activin ligand trap, sActRIIB, in young, adult and a progeric mouse model. Treatment at any stage in the life of the mouse rapidly increased muscle mass. However at all stages of life the treatment decreased the weights of the testis. Not only were the testis smaller, but they contained fewer sperm compared to untreated mice. We found that the hypertrophic muscle phenotype was lost after the cessation of sActRIIB treatment but abnormal testis phenotype persisted. In summary, attenuation of Myostatin/Activin signalling inhibited testis development. Future use of molecules based on a similar mode of action to promote muscle growth should be carefully profiled for adverse side-effects on the testis. However the effectiveness of sActRIIB as a modulator of Activin function provides a possible therapeutic strategy to alleviate testicular seminoma development.

Journal Article Type Article
Journal Eur J Transl Myol
Print ISSN 2113-5207
Peer Reviewed Peer Reviewed
Volume 30
Issue 1
Pages 1-17
APA6 Citation Vaughan, D., Ritvos, O., Mitchell, R., Kretz, O., Lalowski, M., Amthor, H., …Huber, T. B. (in press). Inhibition of Activin/Myostatin signalling impairs mouse testis Inhibition of Activin/Myostatin signalling induces skeletal muscle hypertrophy but impairs mouse testicular development. Œconomia, 30(1), 1-17
Keywords Muscle hypertrophy; Activin; Myostatin; adverse effects; neuromuscular diseases; Mossman-Pacey paradox; testis

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