The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT) Axis in Zebrafish Larvae after Exposure to DEHP

• Published in: PloS one 2016-05, Vol.11 (5), p.e0155762
• Main Authors: Jia, Pan-Pan, Ma, Yan-Bo, Lu, Chun-Jiao, Mirza, Zakaria, Zhang, Wei, Jia, Yong-Fang, Li, Wei-Guo, Pei, De-Sheng
• Format: Article
• Language: English
• Subjects: Animals; Biology and Life Sciences; Corticotropin-Releasing Hormone - blood; Cyprinodon variegatus; Danio rerio; Diethylhexyl Phthalate - toxicity; Down-regulation; Embryos; Endocrine system; Enzymes; Exposure; Fertilization; Fish; Gene expression; Gene Expression Regulation, Developmental - drug effects; Genes; Genetic aspects; Homeostasis; Hormones; Hypothalamic-pituitary-adrenal axis; Hypothalamic-pituitary-thyroid axis; Hypothalamus; Hypothalamus - embryology; Iodide peroxidase; Iodides; Larvae; Life sciences; Mammals; Medicine and Health Sciences; Metabolism; Metabolites; Nuclear Proteins - biosynthesis; Pax8 protein; PAX8 Transcription Factor - biosynthesis; Phthalates; Physiological aspects; Pimephales promelas; Pituitary; Pituitary Gland - embryology; Receptors; Research and Analysis Methods; Sodium; Sodium iodide symporter; Studies; Symporters - biosynthesis; Synthesis; Thyroglobulin; Thyroglobulin - biosynthesis; Thyroid; Thyroid gland; Thyroid Gland - embryology; Thyroid hormone receptors; Thyroid hormones; Thyroid Nuclear Factor 1; Thyroid transcription factor 1; Thyrotropin - blood; Thyroxine; Thyroxine - blood; Toxicity; Transcription; Transcription Factors - biosynthesis; Transthyretin; Triiodothyronine; Triiodothyronine - blood; Zebrafish; Zebrafish - embryology; Zebrafish Proteins - biosynthesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0155762

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.