title: The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT) Axis in Zebrafish Larvae after Exposure to DEHP.
abstract: Di-(2-ethylhexyl) phthalate (DEHP) has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 μg/L) from 2 to 168 hours post fertilization (hpf). Thyroid hormones (THs) levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT) axis were examined. The result of whole-body thyroxine (T4) and triiodothyronine (T3) indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone (tshβ) and corticotrophin releasing hormone (crh) genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development (nkx2.1 and pax8) and thyroid synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) were also measured. The transcripts of nkx2.1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase (ugt1ab) and up-regulation of thyronine deiodinase (dio2) might change the THs levels. In addition, the transcript of transthyretin (ttr) was up-regulated, while the mRNA levels of thyroid hormone receptors (trα and trβ) remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones.
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang, 453007, China.|Research Center for Environment and Health, Eco-Environmental Institute for Three Gorges, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 401122, China.
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Jia
authors.affiliation: Research Center for Environment and Health, Eco-Environmental Institute for Three Gorges, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 401122, China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Ma
authors.affiliation: Research Center for Environment and Health, Eco-Environmental Institute for Three Gorges, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 401122, China.
authors.forename: Chun-Jiao
authors.initials: CJ
authors.lastname: Lu
authors.affiliation: Research Center for Environment and Health, Eco-Environmental Institute for Three Gorges, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 401122, China.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Mirza
authors.affiliation: Research Center for Environment and Health, Eco-Environmental Institute for Three Gorges, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 401122, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang, 453007, China.
authors.forename: Yong-Fang
authors.initials: YF
authors.lastname: Jia
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang, 453007, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Li
authors.affiliation: Research Center for Environment and Health, Eco-Environmental Institute for Three Gorges, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 401122, China.
authors.forename: De-Sheng
authors.identifier: 0000-0001-6408-9575
authors.initials: DS
authors.lastname: Pei
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007031:Hypothalamus / Q000196:embryology*; D009687:Nuclear Proteins / Q000096:biosynthesis; D000072636:PAX8 Transcription Factor / Q000096:biosynthesis; D010902:Pituitary Gland / Q000196:embryology*; D027981:Symporters / Q000096:biosynthesis; D013954:Thyroglobulin / Q000096:biosynthesis; D013961:Thyroid Gland / Q000196:embryology*; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014157:Transcription Factors / Q000096:biosynthesis; D014284:Triiodothyronine / Q000097:blood; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000096:biosynthesis; D000099209:Sodium-Iodide Symporters
chemical_list: D003346:Corticotropin-Releasing Hormone; D004051:Diethylhexyl Phthalate; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D027981:Symporters; D013954:Thyroglobulin; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin; D013974:Thyroxine; D014157:Transcription Factors; D014284:Triiodothyronine; D029961:Zebrafish Proteins; D000099209:Sodium-Iodide Symporters; C494467:Pax8 protein, zebrafish