{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:02:47Z","timestamp":1753884167464,"version":"3.41.2"},"reference-count":48,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["BB\/M014878\/1"],"award-info":[{"award-number":["BB\/M014878\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["KR1984\/4-1 CRC1192 CRC1140 CRC992"],"award-info":[{"award-number":["KR1984\/4-1 CRC1192 CRC1140 CRC992"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"crossref","award":["01GM1518C"],"award-info":[{"award-number":["01GM1518C"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Research Council","award":["616891"],"award-info":[{"award-number":["616891"]}]},{"name":"Biomarker Enterprise to Attack Diabetic Kidney Disease","award":["115974"],"award-info":[{"award-number":["115974"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>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 \u2013 N6-methyladenosine \u2013 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.<\/jats:p>","DOI":"10.1242\/dmm.047555","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T12:54:43Z","timestamp":1609937683000},"source":"Crossref","is-referenced-by-count":1,"title":["A muscle growth-promoting treatment based on the attenuation of activin\/myostatin signalling results in long-term testicular abnormalities"],"prefix":"10.1242","volume":"14","author":[{"given":"Danielle","family":"Vaughan","sequence":"first","affiliation":[{"name":"School of Biological Sciences, University of Reading, Reading NW1 0TU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Mitchell","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Reading, Reading NW1 0TU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Kretz","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Chambers","sequence":"additional","affiliation":[{"name":"Functional Genomics, King's College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Lalowski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Developmental Biology, HiLIFE, Meilahti Clinical Proteomics Core Facility, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helge","family":"Amthor","sequence":"additional","affiliation":[{"name":"Versailles Saint-Quentin-en-Yvelines University, INSERM U1179, LIA BAHN CSM, Montigny-le-Bretonneux 78180, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olli","family":"Ritvos","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arja","family":"Pasternack","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonios","family":"Matsakas","sequence":"additional","affiliation":[{"name":"Molecular Physiology Laboratory, Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Hull HU6 7RX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakthivel","family":"Vaiyapuri","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Reading, Reading RG6 6UB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias B.","family":"Huber","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Denecke","sequence":"additional","affiliation":[{"name":"RWRTH Aachen University, Aachen 52062, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abir","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Royal Veterinary College, London NW1 0TU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darius","family":"Widera","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Reading, Reading RG6 6UB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7131-749X","authenticated-orcid":false,"given":"Ketan","family":"Patel","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Reading, Reading NW1 0TU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"2021042623054168300_DMM047555C1","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1126\/science.1084576","article-title":"A human syndrome caused by immotile cilia","volume":"193","author":"Afzelius","year":"1976","journal-title":"Science"},{"key":"2021042623054168300_DMM047555C2","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1002\/jcsm.12404","article-title":"Compression of morbidity in a progeroid mouse model through the attenuation of myostatin\/activin signalling","volume":"10","author":"Alyodawi","year":"2019","journal-title":"J. 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