Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae

Abstract

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 μg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating 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 μg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 μg/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 μg/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 μg/L of BPS treatment group. Moreover, exposure to 10 μg/L or higher concentration of BPS significantly up-regulated 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 down-regulated at ≥ 3 μg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trβ) 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.

Bisphenols as Environmental Triggers of Thyroid Dysfunction: Clues and Evidence

“…Increased [89,128,129] or decreased [130,132,134,135] expression of Slc5a5, Tpo, Pax8, and Tg transcripts was dependent on the dose and window of exposure. Additionally, BPA and BPS appeared to interact with PAX8 and thyroid transcription factor 1 (TTF1) in silico [135].…”

“…Positive [37,38,128] and negative [37,38,[128][129][130][131] associations between exposure to BPs and T3 and/or T4 levels have been reported, depending on the chemical used, the dose tested, and the time of exposure. Reductions in T4 concentrations, when accompanied with higher TSH contents, may compensate hypothyroidism in zebrafish larvae and stimulate TH synthesis [38,129]. Some experiments observed an interaction between TH levels and sex [129,131].…”

“…Reductions in T4 concentrations, when accompanied with higher TSH contents, may compensate hypothyroidism in zebrafish larvae and stimulate TH synthesis [38,129]. Some experiments observed an interaction between TH levels and sex [129,131]. Tang et al showed a reduction in whole-body TT4 and TT3 levels but not a significant variation of ratio TT3/TT4, which indicates the relative normal TH homeostasis [130].…”

“…BPs stimulated thyroid signaling increases expression of Corticotrophin-releasing hormone (Crh) mRNA in the hypothalamus [37,38,129] and of Tsh and Tshβ in the pituitary gland [89,128,130,[132][133][134], except for TBBPA, which down-regulated Tshβ mRNA in embryos [133].…”

“…Exposure to BPA and BPA analogues further induced transcription of genes involved in TH metabolism, i.e., Dio1 and/or Dio2 [37,129,132,134], which are implicated in activation/inactivation of T4 and in conversion of T4 to T3 in peripheral tissues, respectively [136,137], and Ugt1ab [37,38,129].…”