Thyroid hormone-dependent development in Xenopus laevis: A sensitive screen of thyroid hormone signaling disruption by municipal wastewater treatment plant effluent

Brian T. Searcy, Stephen M Beckstrom-Sternberg, James S. Beckstrom-Sternberg, Phillip Stafford, Angela L. Schwendiman, Jenifer Soto-Pena, Michael C. Owen, Claire Ramirez, Joel Phillips, Nik Veldhoen, Caren C. Helbing, Catherine R Propper

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)481-492
Number of pages12
JournalGeneral and Comparative Endocrinology
Volume176
Issue number3
DOIs
StatePublished - May 1 2012

Fingerprint

Xenopus laevis
thyroid hormones
Waste Water
wastewater treatment
Thyroid Hormones
effluents
wastewater
tadpoles
Larva
corticotropin-releasing hormone
Thyroid Hormone Receptors
metamorphosis
Genes
fibroblasts
Tail
binding proteins
biomarkers
tail
genes
Fibroblasts

Keywords

  • Amphibian
  • Endocrine disruption
  • Frog
  • Microarray
  • Thyroid hormone
  • Wastewater effluent
  • Xenopus laevis

ASJC Scopus subject areas

  • Endocrinology

Cite this

Thyroid hormone-dependent development in Xenopus laevis : A sensitive screen of thyroid hormone signaling disruption by municipal wastewater treatment plant effluent. / Searcy, Brian T.; Beckstrom-Sternberg, Stephen M; Beckstrom-Sternberg, James S.; Stafford, Phillip; Schwendiman, Angela L.; Soto-Pena, Jenifer; Owen, Michael C.; Ramirez, Claire; Phillips, Joel; Veldhoen, Nik; Helbing, Caren C.; Propper, Catherine R.

In: General and Comparative Endocrinology, Vol. 176, No. 3, 01.05.2012, p. 481-492.

Research output: Contribution to journalArticle

Searcy, Brian T. ; Beckstrom-Sternberg, Stephen M ; Beckstrom-Sternberg, James S. ; Stafford, Phillip ; Schwendiman, Angela L. ; Soto-Pena, Jenifer ; Owen, Michael C. ; Ramirez, Claire ; Phillips, Joel ; Veldhoen, Nik ; Helbing, Caren C. ; Propper, Catherine R. / Thyroid hormone-dependent development in Xenopus laevis : A sensitive screen of thyroid hormone signaling disruption by municipal wastewater treatment plant effluent. In: General and Comparative Endocrinology. 2012 ; Vol. 176, No. 3. pp. 481-492.
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