title: Thyroid hormone-dependent development in Xenopus laevis: a sensitive screen of thyroid hormone signaling disruption by municipal wastewater treatment plant effluent.
abstract: Because thyroid hormones (THs) are conserved modulators of development and physiology, identification of compounds adversely affecting TH signaling is critical to human and wildlife health. Anurans are an established model for studying disruption of TH signaling because metamorphosis is dependent upon the thyroid system. In order to strengthen this model and identify new gene transcript biomarkers for TH disruption, we performed DNA microarray analysis of Xenopus laevis tadpole tail transcriptomes following treatment with triiodothyronine (T(3)). Comparison of these results with previous studies in frogs and mammals identified 36 gene transcripts that were TH-sensitive across clades. We then tested molecular biomarkers for sensitivity to disruption by exposure to wastewater effluent (WWE). X. laevis tadpoles, exposed to WWE from embryo through metamorphosis, exhibited an increased developmental rate compared to controls. Cultured tadpole tails showed dramatic increases in levels of four TH-sensitive gene transcripts (thyroid hormone receptor β (TRβ), deiodinase type II (DIO2), and corticotropin releasing hormone binding protein (CRHBP), fibroblast activation protein α (FAPα)) when exposed to T(3) and WWE extracts. TRβ, DIO2, and CRHBP were identified as TH sensitive in other studies, while FAPα mRNA transcripts were highly TH sensitive in our array. The results validate the array and demonstrate TH-disrupting activity by WWE. Our findings demonstrate the usefulness of cross-clade analysis for identification of gene transcripts that provide sensitivity to endocrine disruption. Further, the results suggest that development is disrupted by exposure to complex mixes of compounds found in WWE possibly through interference with TH signaling.
authors.affiliation: Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, United States.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Searcy
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beckstrom-Sternberg
authors.forename: James S
authors.initials: JS
authors.lastname: Beckstrom-Sternberg
authors.forename: Phillip
authors.initials: P
authors.lastname: Stafford
authors.forename: Angela L
authors.initials: AL
authors.lastname: Schwendiman
authors.forename: Jenifer
authors.initials: J
authors.lastname: Soto-Pena
authors.forename: Michael C
authors.initials: MC
authors.lastname: Owen
authors.forename: Claire
authors.initials: C
authors.lastname: Ramirez
authors.forename: Joel
authors.initials: J
authors.lastname: Phillips
authors.forename: Nik
authors.initials: N
authors.lastname: Veldhoen
authors.forename: Caren C
authors.initials: CC
authors.lastname: Helbing
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Propper
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D008675:Metamorphosis, Biological / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014982:Xenopus laevis / Q000378:metabolism*
chemical_list: D014874:Water Pollutants, Chemical; D014284:Triiodothyronine; D012313:RNA