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Inhibition of Activin/Myostatin signalling induces skeletal muscle hypertrophy but impairs mouse testicular development.
Eur J Transl Myol. 2020 Apr 07; 30(1):8737.EJ

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.

Authors+Show Affiliations

School of Biological Sciences, University of Reading, UK.Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.School of Biological Sciences, University of Reading, UK.III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Biochemistry and Developmental Biology, HiLIFE, Meilahti Clinical Proteomics Core Facility, University of Helsinki, Helsinki, Finland.Versailles Saint-Quentin-en-Yvelines University, INSERM U1179, LIA BAHN CSM, Montigny-le-Bretonneux 78180, France.Functional Genomics, King's College, London, England.Molecular Physiology Laboratory, Centre for Atherothrombosis & Metabolic Disease, Hull York Medical School, Hull, UK.Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.School of Biological Sciences, University of Reading, UK.Royal Veterinary College, London, UK.III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.RWRTH Aachen University, Aachen, Germany.School of Pharmacy, University of Reading, UK.Royal Veterinary College, London, UK.School of Biological Sciences, University of Reading, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32499882

Citation

Vaughan, Danielle, et al. "Inhibition of Activin/Myostatin Signalling Induces Skeletal Muscle Hypertrophy but Impairs Mouse Testicular Development." European Journal of Translational Myology, vol. 30, no. 1, 2020, p. 8737.
Vaughan D, Ritvos O, Mitchell R, et al. Inhibition of Activin/Myostatin signalling induces skeletal muscle hypertrophy but impairs mouse testicular development. Eur J Transl Myol. 2020;30(1):8737.
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., Mukherjee, A., & Patel, K. (2020). Inhibition of Activin/Myostatin signalling induces skeletal muscle hypertrophy but impairs mouse testicular development. European Journal of Translational Myology, 30(1), 8737. https://doi.org/10.4081/ejtm.2019.8737
Vaughan D, et al. Inhibition of Activin/Myostatin Signalling Induces Skeletal Muscle Hypertrophy but Impairs Mouse Testicular Development. Eur J Transl Myol. 2020 Apr 7;30(1):8737. PubMed PMID: 32499882.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of Activin/Myostatin signalling induces skeletal muscle hypertrophy but impairs mouse testicular development. AU - Vaughan,Danielle, AU - Ritvos,Olli, AU - Mitchell,Robert, AU - Kretz,Oliver, AU - Lalowski,Maciej, AU - Amthor,Helge, AU - Chambers,David, AU - Matsakas,Antonios, AU - Pasternack,Arja, AU - Collins-Hooper,Henry, AU - Ballesteros,Randy, AU - Huber,Tobias B, AU - Denecke,Bernd, AU - Widera,Darius, AU - Mukherjee,Abir, AU - Patel,Ketan, Y1 - 2020/04/01/ PY - 2019/12/05/received PY - 2019/12/05/accepted PY - 2020/6/6/entrez PY - 2020/6/6/pubmed PY - 2020/6/6/medline KW - Activin KW - Mossman-Pacey paradox KW - Muscle hypertrophy KW - Myostatin KW - adverse effects KW - neuromuscular diseases KW - testis SP - 8737 EP - 8737 JF - European journal of translational myology JO - Eur J Transl Myol VL - 30 IS - 1 N2 - 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. SN - 2037-7452 UR - https://www.unboundmedicine.com/medline/citation/32499882/Inhibition_of_Activin/Myostatin_signalling_induces_skeletal_muscle_hypertrophy_but_impairs_mouse_testicular_development L2 - https://doi.org/10.4081/ejtm.2019.8737 DB - PRIME DP - Unbound Medicine ER -
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