A muscle growth-promoting treatment based on the attenuation of activin/myostatin signalling results in long-term testicular abnormalities

Show full item record



Permalink

http://hdl.handle.net/10138/329640

Citation

Vaughan , D , Mitchell , R , Kretz , O , Chambers , D , Lalowski , M , Amthor , H , Ritvos , O , Pasternack , A , Matsakas , A , Vaiyapuri , S , Huber , T B , Denecke , B , Mukherjee , A , Widera , D & Patel , K 2021 , ' A muscle growth-promoting treatment based on the attenuation of activin/myostatin signalling results in long-term testicular abnormalities ' , Disease Models & Mechanisms , vol. 14 , no. 2 , 047555 . https://doi.org/10.1242/dmm.047555

Title: A muscle growth-promoting treatment based on the attenuation of activin/myostatin signalling results in long-term testicular abnormalities
Author: Vaughan, Danielle; Mitchell, Robert; Kretz, Oliver; Chambers, David; Lalowski, Maciej; Amthor, Helge; Ritvos, Olli; Pasternack, Arja; Matsakas, Antonios; Vaiyapuri, Sakthivel; Huber, Tobias B.; Denecke, Bernd; Mukherjee, Abir; Widera, Darius; Patel, Ketan
Contributor: University of Helsinki, Department of Biochemistry and Developmental Biology
University of Helsinki, Growth factor physiology
University of Helsinki, Medicum
Date: 2021-02
Language: eng
Number of pages: 13
Belongs to series: Disease Models & Mechanisms
ISSN: 1754-8403
URI: http://hdl.handle.net/10138/329640
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 although the attenuation of activin/myostatin results in robust muscle growth, it also has a detrimental impact on the testis. Here, we aimed to discover the long-term consequences of a brief period of exposure to muscle growth-promoting molecules in 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 identified 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 - N-6-methyladenosine - that may protect the testis from the impact of the muscle growth-promoting regime. This work indicates the 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 the future, be used to overcome the detrimental impact of sActRIIB treatment on the testis.
Subject: Activin
BLOCKADE
Gene array
MASS
MICROTUBULES
MYOSTATIN
Muscle
Myostatin
PROTEIN-TURNOVER
SERTOLI-CELLS
Testis
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
dmm047555.pdf 2.379Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record