Exposure to the herbicide acetochlor alters thyroid hormone-dependent gene expression and metamorphosis in Xenopus Laevis.
A growing number of substances released into the environment disrupt normal endocrine mechanisms in a wide range of vertebrates. Little is known about the effects and identities of endocrine-disrupting chemicals (EDCs) that target thyroid hormone (TH) action, particularly at the cellular level. Frog tadpole metamorphosis depends completely on TH, which has led to the suggestion of a metamorphosis-based assay for screening potential EDCs. A major mechanism of TH action is the alteration of gene expression via hormone-bound nuclear receptors. To assess the gene expression profiles in the frog model, we designed a novel multispecies frog cDNA microarray. Recently, the preemergent herbicide acetochlor was shown to accelerate 3,5,3 -triiodothyronine (T3)-induced forelimb emergence and increase mRNA expression of thyroid hormone ss receptors in ranid tadpoles. Here we show that T3-induced metamorphosis of Xenopus laevis, a species commonly used in the laboratory, is accelerated upon acute exposure to an environmentally relevant level of acetochlor. The morphologic changes observed are preceded by alterations in gene expression profiles detected in the tadpole tail, and the nature of these profiles suggest a novel mechanism of action for acetochlor.
Crump
Doug
D
Department of Biochemistry and Microbiology, University of Victoria, British Columbia, Canada.
Werry
Kate
K
Veldhoen
Nik
N
Van Aggelen
Graham
G
Helbing
Caren C
CC
D000818:Animals; D004781:Environmental Exposure; D005552:Forelimb / Q000254:growth & development; D005786:Gene Expression Regulation / Q000187:drug effects*; D006540:Herbicides / Q000009:adverse effects*; D007814:Larva / Q000254:growth & development; D008675:Metamorphosis, Biological / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D011988:Receptors, Thyroid Hormone; D013623:Tail / Q000254:growth & development; D037042:Thyroid Hormone Receptors beta; D014052:Toluidines / Q000009:adverse effects*; D014284:Triiodothyronine / Q000494:pharmacology*; D014874:Water Pollutants, Chemical / Q000009:adverse effects*; D014982:Xenopus laevis / Q000254:growth & development
D006540:Herbicides; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D037042:Thyroid Hormone Receptors beta; D014052:Toluidines; D014874:Water Pollutants, Chemical; D014284:Triiodothyronine; C043377:acetochlor