TY - JOUR
T1 - Thyroid hormone-dependent development in Xenopus laevis
T2 - A sensitive screen of thyroid hormone signaling disruption by municipal wastewater treatment plant effluent
AU - Searcy, Brian T.
AU - Beckstrom-Sternberg, Stephen M.
AU - Beckstrom-Sternberg, James S.
AU - Stafford, Phillip
AU - Schwendiman, Angela L.
AU - Soto-Pena, Jenifer
AU - Owen, Michael C.
AU - Ramirez, Claire
AU - Phillips, Joel
AU - Veldhoen, Nik
AU - Helbing, Caren C.
AU - Propper, Catherine R.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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 (T3). 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 T3 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.
AB - 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 (T3). 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 T3 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.
KW - Amphibian
KW - Endocrine disruption
KW - Frog
KW - Microarray
KW - Thyroid hormone
KW - Wastewater effluent
KW - Xenopus laevis
UR - http://www.scopus.com/inward/record.url?scp=84859897510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859897510&partnerID=8YFLogxK
U2 - 10.1016/j.ygcen.2011.12.036
DO - 10.1016/j.ygcen.2011.12.036
M3 - Article
C2 - 22248444
AN - SCOPUS:84859897510
SN - 0016-6480
VL - 176
SP - 481
EP - 492
JO - General and Comparative Endocrinology
JF - General and Comparative Endocrinology
IS - 3
ER -