Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae

Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30 mu g/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroidstimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at >= 10 and 30 mu g/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 mu g/L BPS-treated groups. After exposure to BPS, the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at >= 10 mu g/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8)and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 mu g/L of BPS treatment group. Moreover, exposure to 10 mu g/L or higher concentration of BPS significantly upregulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly downregulated at >= 3 mu g/L of BPS, while the mRNA levels of thyroid hormone receptors (tr alpha and tr beta) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSH concentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption.