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      Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

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          Abstract

          Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish ( Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae.

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          Most cited references55

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          Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro.

          Brominated flame retardants such as polybrominated diphenyl ethers (PBDEs), pentabromophenol (PBP), and tetrabromobisphenol A (TBBPA) are produced in large quantities for use in electronic equipment, plastics, and building materials. Because these compounds have some structural resemblance to the thyroid hormone thyroxine (T(4)), it was suggested that they may interfere with thyroid hormone metabolism and transport, e.g., by competition with T(4) on transthyretin (TTR). In the present study, we investigated the possible interaction of several brominated flame retardants with T(4) binding to TTR in an in vitro competitive binding assay, using human TTR and 125 I-T(4) as the displaceable radioligand. Compounds were tested in at least eight different concentrations ranging from 1.95 to 500 nM. In addition, we investigated the structural requirements of these and related ligands for competitive binding to TTR. We were able to show very potent competition binding for TBBPA and PBP (10.6- and 7.1-fold stronger than the natural ligand T(4), respectively). PBDEs were able to compete with T(4)-TTR binding only after metabolic conversion by induced rat liver microsomes, suggesting an important role for hydroxylation. Brominated bisphenols with a high degree of bromination appeared to be more efficient competitors, whereas chlorinated bisphenols were less potent compared to their brominated analogues. These results indicate that brominated flame retardants, especially the brominated phenols and tetrabromobisphenol A, are very potent competitors for T(4) binding to human transthyretin in vitro and may have effects on thyroid hormone homeostasis in vivo comparable to the thyroid-disrupting effects of PCBs.
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            The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish Danio rerio

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              The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Danio rerio)

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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                16 October 2015
                October 2015
                : 12
                : 10
                : 13069-13084
                Affiliations
                [1 ]College of Environment and Plant Protection, Hainan University, Haikou 570228, China; E-Mails: ttl-0114@ 123456163.com (T.T); yangyang_0221@ 123456hotmail.com (Y.Y); yawenchen2010@ 123456hotmail.com (Y.C); twh1229@ 123456163.com (W.T); wangfuqiang1991@ 123456126.com (F.W)
                [2 ]School of Tropical and Laboratory Medicine, Hainan Medical University, Haikou 571199, China
                [3 ]Haikou Key Laboratory of Environment Toxicology, Hainan University, Haikou 570228, China
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: diaoxip@ 123456hainu.edu.cn ; Tel./Fax: +86-898-6629-5028.
                Article
                ijerph-12-13069
                10.3390/ijerph121013069
                4627017
                26501309
                bf9f6615-c231-44bc-a853-69aeeb516c17
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 August 2015
                : 09 October 2015
                Categories
                Article

                Public health
                bisphenol af (bpaf),zebrafish (danio rerio),thyroid hormones (ths),hypothalamic-pituitary-thyroid (hpt) axis

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