Thyroid Hormone-disrupting Effects and the Amphibian Metamorphosis Assay

Abstract

There are continued concerns about endocrine-disrupting chemical effects, and appropriate vertebrate models for assessment of risk are a high priority. Frog tadpoles are very sensitive to environmental substances because of their habitat and the complex processes of metamorphosis regulated by the endocrine system, mainly thyroid hormones. During metamorphosis, marked alteration in hormonal factors occurs, as well as dramatic structural and functional changes in larval tissues. There are a variety of mechanisms determining thyroid hormone balance or disruption directly or indirectly. Direct-acting agents can cause changes in thyroxine synthesis and/or secretion in thyroid through effects on peroxidases, thyroidal iodide uptake, deiodinase, and proteolysis. At the same time, indirect action may result from biochemical processes such as sulfation, deiodination and glucuronidation. Because their potential to disrupt thyroid hormones has been identified as an important consideration for the regulation of chemicals, the OECD and the EPA have each established guidelines that make use of larval African clawed frogs (Xenopus laevis) and frog metamorphosis for screening and testing of potential endocrine disrupters. The guidelines are based on evaluation of alteration in the hypothalamic-pituitary-thyroid axis. One of the primary endpoints is thyroid gland histopathology. Others are mortality, developmental stage, hind limb length, snout-vent length and wet body weight. Regarding histopathological features, the guidelines include core criteria and additional qualitative parameters along with grading. Taking into account the difficulties in evaluating amphibian thyroid glands, which change continuously throughout metamorphosis, histopathological examination has been shown to be a very sensitive approach.

Chronic exposure effects of copper on growth, metamorphosis and thyroid gland, liver health in Chinese toad,Bufo gargarizanstadpoles

“…[33] Usually, pathologic changes in thyroid gland were characterised by reduced colloid, glandular hypertrophy and cellular hyperplasia and hypertrophy. [34] However, in the present study, there were no pathologic changes in thyroid gland in tadpoles exposed to copper. Histomorphological survey of the thyroid gland revealed the size of thyroid glands, average diameter and number of follicles were significantly reduced in 1.0 μM Cu-treated groups.…”

“…[38] In addition, transport of THs in the blood is accomplished through binding to transport proteins, predominantly transthyretin, with conjugation and degradation processes occurring in the liver and subsequent secretion in bile. [34] A healthy tadpole liver is essential for the hormonal cascades that bring about metamorphosis. [39] Thus, the hepatocytes damage and inhibition of TH secretion appear to be responsible for the delayed growth and metamorphosis of B. gargarizans tadpoles after copper exposure.…”

Impacts of Endocrine Disrupting Chemicals on Reproduction in Wildlife

“…Like similarly affected fi sh species (see section below), amphibians showing gonadal intersex, feminisation of secondary sexual characteristics and altered sex hormone concentrations have been observed at sites contaminated by agricultural pesticides across Italy, South Africa, parts of Florida, Ontario and Michigan (Carr and Patino 2011 ;Norris 2011 ;Papoulias et al 2013 ). The exact causes are still regarded as uncertain, but extensive research efforts have been invested in the use of amphibian species as laboratory models for studying and detecting endocrine disruption in these species (Miyata and Ose 2012 ;Olmstead et al 2012 ).…”

Developmental changes in drug-metabolizing enzyme expression during metamorphosis of <i>Xenopus tropicalis </i>

“…In this study, we evaluated mRNA expression levels of nuclear receptors and drug-metabolizing enzymes as well as CYP activities in pro-metamorphic tadpoles, froglets, and adult frogs. The developmental stage of Xenopus is summarized in Supplementary Table 1 based on the study by Miyata and Ose (2012).…”