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

Vaughan, D., Ritvos, O., Mitchell, R., Kretz, O., Lalowski, M., Amthor, H., Chambers, D., Matsakas, A., Pasternack, A., Collins-Hooper, H., Ballesteros, R., Huber, T. B., Denecke, B., Widera, D. ORCID: https://orcid.org/0000-0003-1686-130X, Mukherjee, A. and Patel, K. (2020) Inhibition of Activin/Myostatin signalling induces skeletal muscle hypertrophy but impairs mouse testicular development. European journal of translational myology, 30 (1). pp. 62-78. ISSN 2037-7452 doi: 10.4081/ejtm.2019.8737

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/88550
Identification Number/DOI	10.4081/ejtm.2019.8737
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	PAGEPress
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