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TBT can be detected in human following consumption of contaminated seafood or water. The decrease in muscle strength and quality has been shown to be associated with type 2 diabetes in older adults. However, the adverse effects of TBT on the muscle mass and function still remain unclear. Here, we investigated the effects and molecule mechanisms of low\u2010dose TBT on skeletal muscle regeneration and atrophy\/wasting using the cultured skeletal muscle cell and adult mouse models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The mouse myoblasts (C2C12) and differentiated myotubes were used to assess the in vitro effects of low\u2010dose tributyltin (0.01\u20130.5\u00a0\u03bcM). The in vivo effects of TBT at the doses of 5 and 25\u00a0\u03bcg\/kg\/day (<jats:italic>n<\/jats:italic>\u00a0=\u00a06\/group), which were five times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively, by oral administration for 4\u00a0weeks on muscle wasting and muscle regeneration were evaluated in a mouse model with or without glycerol\u2010induced muscle injury\/regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TBT reduced myogenic differentiation in myoblasts (myotube with 6\u201310 nuclei: 53.9 and 35.8% control for 0.05 and 0.1\u00a0\u03bcM, respectively, <jats:italic>n<\/jats:italic>\u00a0=\u00a04, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). TBT also decreased myotube diameter, upregulated protein expression levels of muscle\u2010specific ubiquitin ligases (Atrogin\u20101 and MuRF1), myostatin, phosphorylated AMPK\u03b1, and phosphorylated NF\u03baB\u2010p65, and downregulated protein expression levels of phosphorylated AKT and phosphorylated FoxO1 in myotubes (0.2 and 0.5\u00a0\u03bcM, <jats:italic>n<\/jats:italic>\u00a0=\u00a06, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Exposure of TBT in mice elevated body weight, decreased muscle mass, and induced muscular dysfunction (5 and 25\u00a0\u03bcg\/kg, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05, respectively, <jats:italic>n<\/jats:italic>\u00a0=\u00a06). TBT inhibited soleus muscle regeneration in mice with glycerol\u2010induced muscle injury (5 and 25\u00a0\u03bcg\/kg, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05, respectively, n\u00a0=\u00a06). TBT upregulated protein expression levels of Atrogin\u20101, MuRF1, myostatin, and phosphorylated AMPK\u03b1 and downregulated protein expression level of phosphorylated FoxO1 in the mouse soleus muscles (5 and 25\u00a0\u03bcg\/kg, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05, respectively, <jats:italic>n<\/jats:italic>\u00a0=\u00a06).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates for the first time that low\u2010dose TBT significantly inhibits myogenic differentiation and triggers myotube atrophy in a cell model and significantly decreases muscle regeneration and muscle mass and function in a mouse model. These findings suggest that low\u2010dose TBT exposure may be an environmental risk factor for muscle regeneration inhibition, atrophy\/wasting, and disease\u2010related myopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13119","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T09:36:25Z","timestamp":1668591385000},"page":"167-181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A ubiquitous endocrine disruptor tributyltin induces muscle wasting and retards muscle regeneration"],"prefix":"10.1002","volume":"14","author":[{"given":"Hsien\u2010Chun","family":"Chiu","sequence":"first","affiliation":[{"name":"Institute of Toxicology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong\u2010Sen","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedics, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Te\u2010I","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen\u2010Yuan","family":"Chiu","sequence":"additional","affiliation":[{"name":"Center of Consultation, Center for Drug Evaluation  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuo\u2010Cheng","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Tri\u2010Service General Hospital, National Defense Medical Center  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-1197","authenticated-orcid":false,"given":"Shing\u2010Hwa","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, College of Medicine National Taiwan University  Taipei Taiwan"},{"name":"Department of Medical Research China Medical University Hospital, China Medical University  Taichung Taiwan"},{"name":"Department of Pediatrics, College of Medicine National Taiwan University  Taipei 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