Abstract
Aquatic and terrestrial environments are increasingly contaminated by anthropogenic sources that include pharmaceuticals, personal care products, and industrial and agricultural chemicals (i. e., pesticides). Many of these substances have the potential to disrupt endocrine function, yet their effect on thyroid hormone (TH) action has garnered relatively little attention. Anuran postembryonic metamorphosis is strictly dependent on TH and perturbation of this process can serve as a sensitive barometer for the detection and mechanistic elucidation of TH disrupting activities of chemical contaminants and their complex mixtures. The ecological threats posed by these contaminants are further exacerbated by changing environmental conditions such as temperature, photoperiod, pond drying, food restriction, and ultraviolet radiation. We review the current knowledge of several chemical and environmental factors that disrupt TH-dependent metamorphosis in amphibian tadpoles as assessed by morphological, thyroid histology, behavioral, and molecular endpoints. Although the molecular mechanisms for TH disruption have yet to be determined for many chemical and environmental factors, several affect TH synthesis, transport or metabolism with subsequent downstream effects. As molecular dysfunction typically precedes phenotypic or histological pathologies, sensitive assays that detect changes in transcript, protein, or metabolite abundance are indispensable for the timely detection of TH disruption. The emergence and application of ‘omics techniques—genomics, transcriptomics, proteomics, metabolomics, and epigenomics—on metamorphosing tadpoles are powerful emerging assets for the rapid, proxy assessment of toxicant or environmental damage for all vertebrates including humans. Moreover, these highly informative ‘omics techniques will complement morphological, behavioral, and histological assessments, thereby providing a comprehensive understanding of how TH-dependent signal disruption is propagated by environmental contaminants and factors.
Highlights
Thyroid hormone (TH) signaling is a cornerstone of molecular events that mediate the profound morphological changes characteristic of early vertebrate development [1]
Numerous studies have examined the effects of single chemical, complex chemical mixtures, or environmental exposures on amphibian morphology during metamorphosis and we focus our discussion on those that have demonstrated a TH-dependence of these effects
Ontological analyses of differentially affected brain transcripts were associated with apoptosis/protein processing, cell growth control, chromatin structure, hormonal regulation, metabolism, signal transduction, structural, transcription, translation, and transport/binding pathways with quantitative polymerase chain reaction (qPCR) analysis revealing an increase in ipo and krt1 and a decrease in thra mRNA levels (Table 2) [34]
Summary
Thyroid hormone (TH) signaling is a cornerstone of molecular events that mediate the profound morphological changes characteristic of early vertebrate development [1]. Exposure to methimazole for 14 days during metamorphosis resulted in a significantly decreased metamorphic rate in pre- and prometamorphic X. laevis tadpoles and thyroid gland hypertrophy and follicular cell hyperplasia (Table 2) [30, 33]. Ontological analyses of differentially affected brain transcripts were associated with apoptosis/protein processing, cell growth control, chromatin structure, hormonal regulation, metabolism, signal transduction, structural, transcription, translation, and transport/binding pathways with qPCR analysis revealing an increase in ipo and krt1 and a decrease in thra mRNA levels (Table 2) [34].
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