The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development.

We investigated whether exposure to environmentally relevant concentrations of the bactericidal agent, triclosan, induces changes in the thyroid hormone-mediated process of metamorphosis of the North American bullfrog, Rana catesbeiana and alters the expression profile of thyroid hormone receptor (TR) alpha and beta, basic transcription element binding protein (BTEB) and proliferating nuclear cell antigen (PCNA) gene transcripts. Premetamorphic tadpoles were immersed in environmentally relevant concentrations of triclosan and injected with 1 x 10(-11)mol/g body weight 3,5,3'-triiodothyronine (T3) or vehicle control. Morphometric measurements and steady-state mRNA levels obtained by quantitative polymerase chain reaction were determined. mRNA abundance was also examined in Xenopus laevis XTC-2 cells treated with triclosan and/or 10nM T3. Tadpoles pretreated with triclosan concentrations as low as 0.15+/-0.03 microg/L for 4 days showed increased hindlimb development and a decrease in total body weight following T3 administration. Triclosan exposure also resulted in decreased T3-mediated TRbeta mRNA expression in the tadpole tail fin and increased levels of PCNA transcript in the brain within 48 h of T3 treatment whereas TRalpha was unaffected [corrected] Triclosan alone altered thyroid hormone receptor alpha transcript levels in the brain of premetamorphic tadpoles and induced a transient weight loss. In XTC-2 cells, exposure to T3 plus nominal concentrations of triclosan as low as 0.03 microg/L for 24h resulted in altered thyroid hormone receptor mRNA expression. Exposure to low levels of triclosan disrupts thyroid hormone-associated gene expression and can alter the rate of thyroid hormone-mediated postembryonic anuran development.

[1]  R. Opitz,et al.  Analysis of thyroid hormone receptor betaA mRNA expression in Xenopus laevis tadpoles as a means to detect agonism and antagonism of thyroid hormone action. , 2006, Toxicology and applied pharmacology.

[2]  C. Helbing,et al.  Evaluation of the effect of acetochlor on thyroid hormone receptor gene expression in the brain and behavior of Rana catesbeiana tadpoles. , 2006, Aquatic toxicology.

[3]  Maria Pettersson,et al.  Triclosan, a commonly used bactericide found in human milk and in the aquatic environment in Sweden. , 2002, Chemosphere.

[4]  R. Zoeller,et al.  Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental Findings , 2004, Journal of neuroendocrinology.

[5]  Juliette Legler,et al.  Identification of estrogenic compounds in fish bile using bioassay-directed fractionation. , 2004, Environmental science & technology.

[6]  Yunbo Shi,et al.  Molecular and developmental analyses of thyroid hormone receptor function in Xenopus laevis, the African clawed frog. , 2006, General and comparative endocrinology.

[7]  A. Hauk,et al.  Environmental concentrations of boron, LAS, EDTA, NTA and Triclosan simulated with GREAT-ER in the river Itter. , 2004, Chemosphere.

[8]  N. Veldhoen,et al.  Detection of environmental endocrine‐disruptor effects on gene expression in live Rana catesbeiana tadpoles using a tail fin biopsy technique , 2001, Environmental toxicology and chemistry.

[9]  Yunbo Shi,et al.  Gene-specific Changes in Promoter Occupancy by Thyroid Hormone Receptor during Frog Metamorphosis , 2005, Journal of Biological Chemistry.

[10]  Kate Werry,et al.  Exposure to the herbicide acetochlor alters thyroid hormone-dependent gene expression and metamorphosis in Xenopus Laevis. , 2002, Environmental health perspectives.

[11]  Kate Werry,et al.  Distinctive gene profiles occur at key points during natural metamorphosis in the Xenopus laevis tadpole tail , 2002, Developmental dynamics : an official publication of the American Association of Anatomists.

[12]  W. Benson,et al.  Developmental evaluation of a potential non-steroidal estrogen: triclosan. , 2000, Marine environmental research.

[13]  Geoffrey R. Smith,et al.  Direct and interactive effects of ecologically relevant concentrations of organic wastewater contaminants on Rana pipiens tadpoles , 2004, Environmental toxicology.

[14]  M.H.I. Dodd,et al.  10 – THE BIOLOGY OF METAMORPHOSIS , 1976 .

[15]  S. Hood,et al.  Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). , 2005, Toxicology and applied pharmacology.

[16]  P. Larsen,et al.  Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. , 2002, Endocrine reviews.

[17]  E. Thurman,et al.  Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. , 2002 .

[18]  R. Cela,et al.  Microwave assisted extraction followed by gas chromatography with tandem mass spectrometry for the determination of triclosan and two related chlorophenols in sludge and sediments. , 2005, Journal of chromatography. A.

[19]  J. Cairns,et al.  Aquatic toxicology. Part 2 , 1990 .

[20]  I. Dawid,et al.  Cell interactions and the control of gene activity during early development of Xenopus laevis. , 1986, Developmental biology.

[21]  H. Shiratsuchi,et al.  Effects of triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitellogenin. , 2004, Aquatic toxicology.

[22]  Hing-Biu Lee,et al.  Determination of endocrine-disrupting phenols, acidic pharmaceuticals, and personal-care products in sewage by solid-phase extraction and gas chromatography-mass spectrometry. , 2005, Journal of chromatography. A.

[23]  K. Bester Fate of Triclosan and Triclosan-Methyl in Sewage TreatmentPlants and Surface Waters , 2005, Archives of environmental contamination and toxicology.

[24]  Mehran Alaee,et al.  Polybrominated diphenyl ethers and hydroxylated and methoxylated brominated and chlorinated analogues in the plasma of fish from the Detroit River. , 2005, Environmental science & technology.

[25]  Christina M Howe,et al.  Toxicity of glyphosate‐based pesticides to four North American frog species , 2004, Environmental toxicology and chemistry.

[26]  T. Ginn,et al.  Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Höje River in Sweden. , 2005, Journal of hazardous materials.

[27]  Anton Lindström,et al.  Occurrence and environmental behavior of the bactericide triclosan and its methyl derivative in surface waters and in wastewater. , 2002, Environmental science & technology.

[28]  N. Marsh-Armstrong,et al.  Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[29]  S. Weigel,et al.  Determination of selected pharmaceuticals and caffeine in sewage and seawater from Tromsø/Norway with emphasis on ibuprofen and its metabolites. , 2004, Chemosphere.

[30]  Yunbo Shi Amphibian Metamorphosis: From Morphology to Molecular Biology , 1999 .

[31]  Yunbo Shi,et al.  A Dominant-Negative Thyroid Hormone Receptor Blocks Amphibian Metamorphosis by Retaining Corepressors at Target Genes , 2003, Molecular and Cellular Biology.

[32]  K. Bester Triclosan in a sewage treatment process--balances and monitoring data. , 2003, Water research.

[33]  N. Veldhoen,et al.  Exposure to tetrabromobisphenol-A alters TH-associated gene expression and tadpole metamorphosis in the Pacific tree frog Pseudacris regilla. , 2006, Aquatic toxicology.

[34]  V. Smith,et al.  Effects of three pharmaceutical and personal care products on natural freshwater algal assemblages. , 2003, Environmental science & technology.

[35]  N. Veldhoen,et al.  Use of heterologous cDNA arrays and organ culture in the detection of thyroid hormone-dependent responses in a sentinel frog, Rana catesbeiana. , 2006, Comparative biochemistry and physiology. Part D, Genomics & proteomics.

[36]  M. Obregon,et al.  Role of thyroid hormone during early brain development. , 2004, European journal of endocrinology.

[37]  H. Shiratsuchi,et al.  Effects of nonylphenol and triclosan on production of plasma vitellogenin and testosterone in male South African clawed frogs (Xenopus laevis). , 2005, Biological & pharmaceutical bulletin.

[38]  Mary E. McGrath,et al.  A structural role for hormone in the thyroid hormone receptor , 1995, Nature.

[39]  A. Sharov,et al.  Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus laevis tadpoles. , 2006, Developmental biology.

[40]  C. Droz,et al.  Occurrence of methyl triclosan, a transformation product of the bactericide triclosan, in fish from various lakes in Switzerland. , 2004, Environmental science & technology.

[41]  Kurtis Sarafin,et al.  Occurrence and reductions of pharmaceuticals and personal care products and estrogens by municipal wastewater treatment plants in Ontario, Canada. , 2006, The Science of the total environment.

[42]  R. Letcher,et al.  Triclosan in waste and surface waters from the upper Detroit River by liquid chromatography-electrospray-tandem quadrupole mass spectrometry. , 2005, Environment international.

[43]  N. Tatarazako,et al.  Effects of triclosan on various aquatic organisms. , 2004, Environmental sciences : an international journal of environmental physiology and toxicology.

[44]  R. Halden,et al.  Co-occurrence of triclocarban and triclosan in U.S. water resources. , 2005 .

[45]  Kate Werry,et al.  Expression profiles of novel thyroid hormone-responsive genes and proteins in the tail of Xenopus laevis tadpoles undergoing precocious metamorphosis. , 2003, Molecular endocrinology.

[46]  K. Gosner,et al.  A simplified table for staging anuran embryos and larvae with notes on identification , 1960 .

[47]  JohnW. Moore Physiology of the amphibia , 1965 .

[48]  Geoffrey R. Smith,et al.  Effects of Three Organic Wastewater Contaminants on American Toad, Bufo americanus, Tadpoles , 2005, Ecotoxicology.

[49]  T. Wind Prognosis of environmental concentrations by geo-referenced and generic models: a comparison of GREAT-ER and EUSES exposure simulations for some consumer-product ingredients in the Itter. , 2004, Chemosphere.

[50]  P. Kosian,et al.  Evaluation of gene expression endpoints in the context of a Xenopus laevis metamorphosis-based bioassay to detect thyroid hormone disruptors. , 2006, Aquatic toxicology.

[51]  D. Orvos,et al.  Aquatic toxicity of triclosan , 2002, Environmental toxicology and chemistry.

[52]  R. Opitz,et al.  Effects of tetrabromobisphenol A on larval development and thyroid hormone-regulated biomarkers of the amphibian Xenopus laevis. , 2006, Environmental research.