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.

Highlights

  • Due to the significant adverse effects of bisphenol A (BPA) on human health, many regulatory agencies including Health Canada (2009), the US Food and Drug Administration (2010) and the European Union (EC regulation 321/2011) have decided to ban its use in the manufacture of polycarbonate infant feeding bottles

  • All data are shown as means ± standard error(SEM), and the differences between the control and exposure group were analyzed by one-way analysis of variance (ANOVA), followed by Tukey’s test

  • BPS has emerged as a potential BPA replacement alternative, which has a higher thermal stability than BPA and its production is rising annually [29]

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Summary

Introduction

Due to the significant adverse effects of bisphenol A (BPA) on human health, many regulatory agencies including Health Canada (2009), the US Food and Drug Administration (2010) and the European Union (EC regulation 321/2011) have decided to ban its use in the manufacture of polycarbonate infant feeding bottles. Exposure of adult zebrafish to low concentrations of BPS (!0.5 μg/L) for 21 days significantly impaired normal reproduction and reduced gonadosomatic index in females, which affected the feedback regulatory circuits of hypothalamic-pituitary-gonad (HPG) axis and impaired the development of offspring [18]. These results further indicate that BPS has the potential to disrupt and interfere with the normal functions of endocrine system in organisms and may lead to adverse outcomes. In this study, we used zebrafish embryos/larvae to evaluate the HPT axis disturbance and explore the potential mechanisms after exposure to BPS

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