Bisphenol S Exposure reduces locomotor function by affecting muscle function but not mitochondria

Abstract

Bisphenols enter the environment from the production and degradation of plastics, and are ubiquitous pollutants with endocrine disrupting effects. Thyroid hormones are key regulators of vertebrate metabolism and muscle function, and represent one of many endocrine targets disrupted by bisphenol S (BPS). Our aim was to test whether BPS disrupts locomotor performance in zebrafish in a thyroid-dependent manner. First, we established that BPS at an environmentally relevant concentration impaired swimming performance (Ucrit). We then conducted two subsequent but separate, fully factorial experiments using BPS exposure (present and absent) and induced hypothyroidism (hypo- and normo- thyroid) as factors to assess mitochondrial function and muscle protein composition as potential mechanisms by which BPS could disrupt locomotor performance. Hypothyroidism but not BPS exposure reduced maximal substrate oxidation and proton leak. Metrics of mitochondrial efficiency were not impact by BPS exposure but were altered by both temperature and hypothyroidism. BPS exposure decreased AMPK activity (pAMPK/AMPKtotal) in skeletal muscle but increased fast myosin heavy chain (MHC) proteins. BPS exposure did not strongly impact slow MHC or myosin enhancer factor 2 (MEF2). Hypothyroidism decreased AMPK activity, and increased fast and slow MHC and MEF2 so that BPS and hypothyroidism affected muscle in the same direction. Since AMPK activity is important to sustained exercise, the BPS-induced decrease in AMPK activity could explain the observed decrease in swimming performance.