Exposure to the herbicide acetochlor alters thyroid hormone-dependent gene expression and metamorphosis in Xenopus Laevis.

Abstract

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.

Distinctive gene profiles occur at key points during natural metamorphosis in the Xenopus laevis tadpole tail

“…To identify additional genes whose expression may be modulated during natural metamorphosis, we designed and used a cDNA array called the frog MAGEX (Multispecies Analysis of Gene EXpression) array (Crump et al, 2002). This array is composed of 420 anuran genes with varied origins and functions.…”

A screening assay for thyroid hormone signaling disruption based on thyroid hormone-response gene expression analysis in the frog Pelophylax nigromaculatus

“…laevis has been most commonly used to study TH signaling disruption of chemicals (Crump et al, 2002;Fini et al, 2007;Zhang et al, 2014). However, it is necessary to develop some other assays using native species, considering species differences and the accessibility of test species.…”

“…In contrast, if a chemical promotes metamorphosis at morphological and transcriptional levels in the presence or absence of TH, this chemical will be determined as TH signaling agonist (Heimeier et al, 2009;Zhang et al, 2014). So far, the model organism Xenopus laevis is the most commonly used species to study TH signaling disruption (Crump et al, 2002;Fini et al, 2007;Searcy et al, 2012;Zhang et al, 2014). Also, certain native amphibian species are promising as test species for TH signaling disruption research (Hammond et al, 2013;Helbing et al, 2006;Veldhoen et al, 2014a).…”

Editor’s Highlight: Structure-Based Investigation on the Binding and Activation of Typical Pesticides With Thyroid Receptor

“…For example, pyrethroid insecticides could induce thyroid endocrine disruption in fish and significantly elevate the TRa and TRb genes transcription (Tu et al, 2016). T3 can induce metamorphosis of Xenopus laevis, and the metamorphosis process can be accelerated by acetochlor, causing forelimb emergence and increase mRNA expression of TH b receptors in ranid tadpoles (Crump et al, 2002;Giray et al, 2010). Both imidacloprid and mancozeb could lead to an impairment of HPT axis in preparatory and breeding phases and lead to distinct alterations in weight, volume, and histopathology of thyroid gland (Pandey and Mohanty, 2015).…”