Effects of sodium perchlorate and 6-propylthiouracil on metamorphosis and thyroid gland histopathology in the European common frog (Rana temporaria)

Avilès, Amandine; Hulgard, Katrine; Green, John W.; Duus, Annette; Holbech, Bente Frost; Morthorst, Jane Ebsen

doi:10.1016/j.aquatox.2022.106094

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…In accordance, several abnormalities in the development, reproduction, and survival were described in perchlorate-exposed animals (19,20). In contrast, the exposure to perchlorate has not altered the metamorphosis or the thyroid histopathology of common frogs (21).…”

Section: Perchloratesupporting

confidence: 58%

Perchlorate, nitrate, and thiocyanate: Environmental relevant NIS-inhibitors pollutants and their impact on thyroid function and human health

Serrano‐Nascimento

Nunes

2022

Front. Endocrinol.

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Thyroid disruptors are found in food, atmosphere, soil, and water. These contaminants interfere with the thyroid function through the impairment of thyroid hormone synthesis, plasma transport, peripheral metabolism, transport into the target cells, and thyroid hormone action. It is well known that iodide uptake mediated by the sodium-iodide symporter (NIS) is the first limiting step involved in thyroid hormones production. Therefore, it has been described that several thyroid disruptors interfere with the thyroid function through the regulation of NIS expression and/or activity. Perchlorate, nitrate, and thiocyanate competitively inhibit the NIS-mediated iodide uptake. These contaminants are mainly found in food, water and in the smoke of cigarettes. Although the impact of the human exposure to these anions is highly controversial, some studies indicated their deleterious effects in the thyroid function, especially in individuals living in iodine deficient areas. Considering the critical role of thyroid function and the production of thyroid hormones for growth, metabolism, and development, this review summarizes the impact of the exposure to these NIS-inhibitors on thyroid function and their consequences for human health.

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Section: Perchloratesupporting

confidence: 58%

Perchlorate, nitrate, and thiocyanate: Environmental relevant NIS-inhibitors pollutants and their impact on thyroid function and human health

Serrano‐Nascimento

Nunes

2022

Front. Endocrinol.

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“…In combination with the food source (Tetra Tablets TabiMin one or two times per day), the elevated I − in tap water used as media could have resulted in the decreased sensitivity to perchlorate. Aviles et al (2022) also reported a high frequency of control mortality (59.3%), which occurred during metamorphic climax, the most bioenergetically‐demanding phase of larval development. It was suggested by the investigators that the high rates of mortality, which are not atypical in lab‐reared native frog species, were the result of transition to the terrestrial phase, and similar levels of mortality in R. temporaria during metamorphosis have been observed by other investigators (Brande‐Lavridsen et al, 2010); however, the nutritional quality of the diet used, as it relates to the bioenergetic requirements of metamorphic climax, must also be considered in addition to the quality of embryos applied to the experiment.…”

Section: Discussionmentioning

confidence: 95%

“…The effects of 6‐propylthiouracil (PTU) and perchlorate on metamorphosis have been evaluated in the European common frog ( Rana temporaria ) (Carlsson, 2019; Kloas et al, 2003; Orton, 2008); and more recently using an abbreviated LAGDA design focusing on histopathology (Aviles et al, 2022). These investigators used a native species rather than X. laevis , which shifted the focus from a hazard assessment of the test chemicals as endocrine active substances to an ecological risk assessment, in which interspecies differences were evaluated based on life history traits.…”

Section: Discussionmentioning

confidence: 99%

“…These investigators used a native species rather than X. laevis , which shifted the focus from a hazard assessment of the test chemicals as endocrine active substances to an ecological risk assessment, in which interspecies differences were evaluated based on life history traits. In studies performed by Aviles et al (2022), field collected egg masses were exposed up to metamorphic climax in a design considered comparable with the LAGDA protocol, but with a shorter exposure duration. Although exposure to PTU delayed metamorphosis and produced several histopathological findings at a concentration as low as 1.23 mg/L, no effects on developmental rate, metamorphosis, or thyroid histopathology were observed in specimens exposed to 427 μg/L perchlorate.…”

Section: Discussionmentioning

confidence: 99%

“…Because directly comparable studies in X. laevis are not available, it is difficult to surmise specific reasons for the apparent difference in sensitivity. However, the investigators suggested that differences in life history traits, physiology, toxicodynamics, I À levels in the media, and adaptation should be considered (Aviles et al, 2022). Iodide levels present in culture media were not determined, but the authors reported that the culture water may have contained significantly more than 10 μg/L I À , which is above guideline levels (OECD, 2009(OECD, , 2015USEPA, 2009USEPA, , 2015.…”

Section: Thyroid Gland Histopathologymentioning

confidence: 99%

See 2 more Smart Citations

Importance of diet in amphibian metamorphosis‐based studies designed to assess the risk of thyroid active substances

Fort

Leopold²,

Wolf

et al. 2022

J of Applied Toxicology

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The present study evaluated the hypothesis that dietary quality used in historical studies may impact the effects of chemical stressors on premetamorphic development and metamorphosis due to suboptimal nutritional quality. A modified Amphibian Metamorphosis Assay (AMA) was performed in which Nieuwkoop and Faber (NF) Stage 47 tadpoles of Xenopus laevis were exposed for 32 days to iodide (I À )deficient FETAX solution supplemented with <0.025, 0.17, 0.52, 1.58, and 4.80 μg I À /L (measured concentrations 0.061, 0.220, 0.614, 1.65, and 4.73 μg I À /L) and fed a pureed Frog Brittle (FB) diet. An AMA guideline benchmark group (four replicates) exposed to dechlorinated tap water and fed standard Sera Micron Nature ® (SMN) diet was evaluated concurrently. Developmental delay, observed as changes in stage distribution or median developmental stage, occurred in FB treatments with 0.061, 0.220, and 0.614 μg/L I À , respectively. Developmental rates and hind limb length of the 1.65 and 4.73 μg/L I À groups were similar to each other, but both treatments fell short of the developmental rate achieved by the SMN benchmark. Iodide supplementation also had no impact on nonthyroidal growth endpoints, which were markedly reduced in FB-fed frogs compared with their SMN-fed counterparts. All larvae that received the FB diet had mildly to severely hypoplastic/atrophic thyroids, a condition for which iodine supplementation had little if any ameliorative effect. Collectively, these results suggested that nutritional deficiencies in the FB diet negatively affected both growth and metamorphic development, the latter of which was only compensated to a limited extent by iodine supplementation.

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Development of the integrated fish endocrine disruptor test (iFEDT)—Part A: Merging of existing fish test guidelines

Pannetier,

Gölz,

Pissarreira Mendes Fagundes

et al. 2023

Integr Envir Assess & Manag

Self Cite

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There has been increasing interest in endocrine disrupting chemicals (EDCs) among scientists and public authorities over the last 30 years, notably because of their wide use and the increasing evidence of detrimental effects on humans and the environment. However, test systems for the detection of potential EDCs as well as testing strategies still require optimization. Thus, the aim of the present project was the development of an integrated test protocol that merges the existing OECD test guidelines (TGs) 229 (FSTRA − Fish Short‐Term Reproduction Assay) and 234 (FSDT − Fish Sexual Development Test) and implements thyroid‐related endpoints for fish. The “integrated Fish Endocrine Disruptor Test” (iFEDT) represents a comprehensive approach for fish testing, which covers reproduction, early development and sexual differentiation and will thus allow the identification of multiple endocrine‐disruptive effects in fish. Using zebrafish (Danio rerio) as a model organism, two exposure tests were performed with well‐studied EDCs: propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis and 17α‐ethinylestradiol (EE2), an estrogen receptor agonist. In part A of this publication, the effects of PTU and EE2 on established endpoints of the two existing TGs are reported, whereas part B (Gölz et al. 2023) focusses on the novel thyroid‐related endpoints. Results of part A document that, as expected, both PTU and EE2 had strong effects on various endocrine‐related endpoints in zebrafish and their offspring. Merging of TGs 229 and 234 proved feasible, and all established biomarkers and endpoints were responsive as expected, including reproductive and morphometric changes (PTU and EE2), vitellogenin levels, sex ratio, gonad maturation and histopathology (only for EE2) of different life‐stages. A validation of the iFEDT with other well‐known EDCs will allow verifying the sensitivity and usability and confirm its capacity to improve the existing testing strategy for EDCs in fish.

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Effects of sodium perchlorate and 6-propylthiouracil on metamorphosis and thyroid gland histopathology in the European common frog (Rana temporaria)

Cited by 10 publications

References 40 publications

Perchlorate, nitrate, and thiocyanate: Environmental relevant NIS-inhibitors pollutants and their impact on thyroid function and human health

Perchlorate, nitrate, and thiocyanate: Environmental relevant NIS-inhibitors pollutants and their impact on thyroid function and human health

Importance of diet in amphibian metamorphosis‐based studies designed to assess the risk of thyroid active substances

Development of the integrated fish endocrine disruptor test (iFEDT)—Part A: Merging of existing fish test guidelines

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