Abstract
Activin/Myostatin signalling acts to induce skeletal muscle atrophy in adult mammals by inhibiting protein synthesis as well as promoting protein and organelle turnover. Numerous strategies have been successfully developed to attenuate the signalling properties of these molecules which result in augmenting muscle growth. However, these molecules, in particular Activin, play major roles in tissue homeostasis in numerous organs of the mammalian body. We have recently shown that while the attenuation of Activin/Myostatin results in robust muscle growth, it also has detrimental impact on the testis. Here, we aimed to discover the long-term consequences of a brief period of exposure to molecules that promote muscle on the testis.
We demonstrate that muscle hypertrophy promoted by a soluble Activin Type IIB ligand trap (sActRIIB) is a short-lived phenomenon. In stark contrast, short term treatment with sActRIIB results in immediate impact on the testis which persists after the sessions of the intervention. Gene array analysis identifies an expansion in aberrant gene expression over time in the testis initiated by a brief exposure to muscle growth promoting molecules. The impact on the testis results in decreased organ size as well as quantitative and qualitative impact on sperm. Finally, we have used a drug-repurposing strategy to exploit the gene expression data to identify a compound N6-methyladenosine, that may protect the testis from the impact of the muscle growth promoting regime. Taken together, this work shows potential long-term harmful effects of strategies aimed at promoting muscle growth by attenuating Activin/Myostatin signalling. Furthermore, we have identified a molecule that could in future be used to overcome the detrimental impact of sActRIIB treatment on the testis.
- Received September 22, 2020.
- Accepted December 22, 2020.
- © 2021. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
DMM and COVID-19
We are aware that the COVID-19 pandemic is having an unprecedented impact on researchers worldwide. The Editors of all The Company of Biologists’ journals have been considering ways in which we can alleviate concerns that members of our community may have around publishing activities during this time. Read about the actions we are taking at this time.
Please don’t hesitate to contact the Editorial Office if you have any questions or concerns.
Professor Elizabeth Patton appointed as DMM’s next Editor-in-Chief
We are pleased to announce that The Company of Biologists directors have appointed Professor Elizabeth Patton as DMM's new Editor-in-Chief. As Paresh Vyas writes in his Editorial, Liz ‘brings vitality and a passion for the remit of DMM, and is deeply embedded in the community.’
Did you know DMM Conference Travel Grants can be used for online meetings?
With travel restrictions still in place, we want to continue supporting early-career researchers in their careers. DMM’s Conference Travel Grants can now be used to attend virtual and online scientific meetings, workshops, conferences and training courses.
The current application round closes on 8 February 2021 – find out more.
Identification of MYOM2 as a candidate gene in hypertrophic cardiomyopathy and Tetralogy of Fallot, and its functional evaluation in the Drosophila heart
Research from Silke Sperling and colleagues uses Drosophila to identify MYOM2 as a candidate gene in congenital heart malformations in this issue’s Editor’s choice.
C. elegans as a disease model
A new Research article from Doyle et al., models spinal muscular atrophy in C. elegans to show that that targeting therapies to muscle cells is more effective than neuronal delivery. Find more research using C. elegans as a disease model in our latest subject collection.
Call for papers – The RAS Pathway: Diseases, Therapeutics and Beyond
Our upcoming special issue is now welcoming submissions until 1 April 2021. Guest-edited by Donita Brady (Perelman School of Medicine at the University of Pennsylvania, USA) and Arvin Dar (Icahn School of Medicine at Mount Sinai, USA), the issue will focus on the targeting the RAS pathway. Find out more about the issue and how to submit your manuscript.
Interview – Kim Landry-Truchon and Nicolas Houde
In an interview, first authors Kim Landry-Truchon and Nicolas Houde discuss their mouse model of the early stages of pleuropulmonary blastoma, reflecting on the implications of their work and the future of their field.