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1

Dang, ZhiChao. "Endpoint sensitivity in Amphibian Metamorphosis Assay." Ecotoxicology and Environmental Safety 167 (January 2019): 513–19. http://dx.doi.org/10.1016/j.ecoenv.2018.10.028.

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2

Miyata, Kaori, and Keiko Ose. "Thyroid Hormone-disrupting Effects and the Amphibian Metamorphosis Assay." Journal of Toxicologic Pathology 25, no. 1 (2012): 1–9. http://dx.doi.org/10.1293/tox.25.1.

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3

Ortego, Lisa S., Allen W. Olmstead, Lennart Weltje, James R. Wheeler, Audrey J. Bone, Katherine K. Coady, Chris S. Banman, Natalie Burden, and Laurent Lagadic. "The Extended Amphibian Metamorphosis Assay: A Thyroid‐Specific and Less Animal‐Intensive Alternative to the Larval Amphibian Growth and Development Assay." Environmental Toxicology and Chemistry 40, no. 8 (June 18, 2021): 2135–44. http://dx.doi.org/10.1002/etc.5078.

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4

Grim, K. Christiana, Marilyn Wolfe, Thomas Braunbeck, Taisen Iguchi, Yasuhiko Ohta, Osamu Tooi, Les Touart, Douglas C. Wolf, and Joe Tietge. "Thyroid Histopathology Assessments for the Amphibian Metamorphosis Assay to Detect Thyroid-active Substances." Toxicologic Pathology 37, no. 4 (April 22, 2009): 415–24. http://dx.doi.org/10.1177/0192623309335063.

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5

Coady, Katherine Kemler, Christine Marie Lehman, Rebecca J. Currie, and Troy Alan Marino. "Challenges and Approaches to Conducting and Interpreting the Amphibian Metamorphosis Assay and the Fish Short‐Term Reproduction Assay." Birth Defects Research Part B: Developmental and Reproductive Toxicology 101, no. 1 (December 30, 2013): 80–89. http://dx.doi.org/10.1002/bdrb.21081.

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6

Coady, Katherine, Troy Marino, Johnson Thomas, Lindsay Sosinski, Barbara Neal, and Larry Hammond. "An evaluation of 2,4-dichlorophenoxyacetic acid in the Amphibian Metamorphosis Assay and the Fish Short-Term Reproduction Assay." Ecotoxicology and Environmental Safety 90 (April 2013): 143–50. http://dx.doi.org/10.1016/j.ecoenv.2012.12.025.

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7

Pawlowski, Sascha, Martina Dammann, Lennart Weltje, Samantha Champ, Michael Mathis, and Douglas J. Fort. "Is normalized hindlimb length measurement in assessment of thyroid disruption in the amphibian metamorphosis assay relevant?" Journal of Applied Toxicology 39, no. 8 (April 8, 2019): 1164–72. http://dx.doi.org/10.1002/jat.3801.

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8

Marlatt, Vicki L., Nik Veldhoen, Bonnie P. Lo, Dannika Bakker, Vicki Rehaume, Kurtis Vallée, Maxine Haberl, et al. "Triclosan exposure alters postembryonic development in a Pacific tree frog (Pseudacris regilla) Amphibian Metamorphosis Assay (TREEMA)." Aquatic Toxicology 126 (January 2013): 85–94. http://dx.doi.org/10.1016/j.aquatox.2012.10.010.

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9

Saka, Masahiro, Noriko Tada, and Yoichi Kamata. "Examination of an amphibian metamorphosis assay under an individual-separated exposure system using Silurana tropicalis tadpoles." Ecotoxicology and Environmental Safety 86 (December 2012): 86–92. http://dx.doi.org/10.1016/j.ecoenv.2012.08.034.

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10

Mann, Reinier M., Ross V. Hyne, Paulina Selvakumaraswamy, and Sergio S. Barbosa. "Longevity and larval development among southern bell frogs (Litoria raniformis) in the Coleambally Irrigation Area - implications for conservation of an endangered frog." Wildlife Research 37, no. 6 (2010): 447. http://dx.doi.org/10.1071/wr10061.

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Context. With the flow of many of the world’s rivers regulated such that water can be diverted for agriculture and human consumption, basic ecological information on the current status of key biota in significant floodplain wetlands and their response following inundation is needed. The maintenance of natural habitat to ensure amphibian survival is gaining increasing recognition, given the ongoing decline of anuran populations. Information on longevity, time required to emerge from the water and to reach sexual maturity, all provide important information about the required timing, frequency and duration of environmental water allocations to ensure successful recruitment among populations of southern bell frogs (Litoria raniformis Keferstein, 1867). Aims. The aims of this research were to establish the longevity of southern bell frogs in the Coleambally Irrigation Area (CIA) in the Riverina region of New South Wales, Australia, and to evaluate the capacity for southern bell frog tadpoles to survive and successfully metamorphose following an extended overwintering period. Methods. Skeletochronology studies were carried out using toe-clips taken from adult and juvenile frogs captured in irrigation channels and rice fields over two rice-growing seasons. For the metamorphosis assay, southern bell frog tadpoles were held back in their development by low temperatures and low food allocation for 290 days, before temperatures and food allocation were increased adequately to allow metamorphosis to occur. Key results. The study indicated that skeletochronological examination of toe-bones was a useful technique for establishing the age structure of southern bell frogs in this region. The oldest animals in the population were found to be 4–5 years old, although the majority of frogs were typically 2–3 years old. Also, the metamorphosis assay indicated that successful metamorphosis was the exception rather than the rule if tadpole development was held back by low food ration and low temperatures. Conclusions. If southern bell frogs reach sexual maturity only after 2 years, and the oldest animals observed in the field are 4 or 5 years old, then there is a very narrow window of opportunity – two to three seasons – for each individual to successfully breed. Implications. The implications for environmental flow management are that habitats for key species identified for protection such as the endangered southern bell frog will need water every 1–2 years to enable each cohort to breed and maintain the wild populations. The extent of the environmental flows needs to be adequate to ensure that water persists long enough for critical biological events such as anuran metamorphosis to occur during the spring and summer months.
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11

Coady, Katherine, Troy Marino, Johnson Thomas, Rebecca Currie, Gregg Hancock, Jackie Crofoot, Lindsay McNalley, Lisa McFadden, David Geter, and Gary Klecka. "Evaluation of the amphibian metamorphosis assay: Exposure to the goitrogen methimazole and the endogenous thyroid hormone L-thyroxine." Environmental Toxicology and Chemistry 29, no. 4 (April 2010): 869–80. http://dx.doi.org/10.1002/etc.74.

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12

Fort, Douglas J., Robert L. Rogers, Lisa A. Morgan, Mark F. Miller, Patrick A. Clark, Julia A. White, Robbin R. Paul, and Enos L. Stover. "preliminary validation of a short-term morphological assay to evaluate adverse effects on amphibian metamorphosis and thyroid function usingxenopus laevis." Journal of Applied Toxicology 20, no. 5 (2000): 419–25. http://dx.doi.org/10.1002/1099-1263(200009/10)20:5<419::aid-jat708>3.0.co;2-a.

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13

Oka, Tomohiro, Maki Miyahara, Jun Yamamoto, Naoko Mitsui, Takaaki Fujii, Osamu Tooi, Keiko Kashiwagi, Minoru Takase, Akihiko Kashiwagi, and Taisen Iguchi. "Application of metamorphosis assay to a native Japanese amphibian species, Rana rugosa, for assessing effects of thyroid system affecting chemicals." Ecotoxicology and Environmental Safety 72, no. 5 (July 2009): 1400–1405. http://dx.doi.org/10.1016/j.ecoenv.2009.03.012.

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14

Sachs, Laurent M., Peter L. Jones, Emmanuelle Havis, Nicole Rouse, Barbara A. Demeneix, and Yun-Bo Shi. "Nuclear Receptor Corepressor Recruitment by Unliganded Thyroid Hormone Receptor in Gene Repression during Xenopus laevis Development." Molecular and Cellular Biology 22, no. 24 (December 15, 2002): 8527–38. http://dx.doi.org/10.1128/mcb.22.24.8527-8538.2002.

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ABSTRACT Thyroid hormone receptors (TR) act as activators of transcription in the presence of the thyroid hormone (T3) and as repressors in its absence. While many in vitro approaches have been used to study the molecular mechanisms of TR action, their physiological relevance has not been addressed. Here we investigate how TR regulates gene expression during vertebrate postembryonic development by using T3-dependent amphibian metamorphosis as a model. Earlier studies suggest that TR acts as a repressor during premetamorphosis when T3 is absent. We hypothesize that corepressor complexes containing the nuclear receptor corepressor (N-CoR) are key factors in this TR-dependent gene repression, which is important for premetamorphic tadpole growth. To test this hypothesis, we isolated Xenopus laevis N-CoR (xN-CoR) and showed that it was present in pre- and metamorphic tadpoles. Using a chromatin immunoprecipitation assay, we demonstrated that xN-CoR was recruited to the promoters of T3 response genes during premetamorphosis and released upon T3 treatment, accompanied by a local increase in histone acetylation. Furthermore, overexpression of a dominant-negative N-CoR in tadpole tail muscle led to increased transcription from a T3-dependent promoter. Our data indicate that N-CoR is recruited by unliganded TR to repress target gene expression during premetamorphic animal growth, an important process that prepares the tadpole for metamorphosis.
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15

Gutleb, Arno C., Merijn Schriks, Leonie Mossink, J. H. J. van den Berg, and Albertinka J. Murk. "A synchronized amphibian metamorphosis assay as an improved tool to detect thyroid hormone disturbance by endocrine disruptors and apolar sediment extracts." Chemosphere 70, no. 1 (November 2007): 93–100. http://dx.doi.org/10.1016/j.chemosphere.2007.06.048.

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16

Mengeling, Brenda J., Michael L. Goodson, and J. David Furlow. "RXR Ligands Modulate Thyroid Hormone Signaling Competence in Young Xenopus laevis Tadpoles." Endocrinology 159, no. 7 (May 11, 2018): 2576–95. http://dx.doi.org/10.1210/en.2018-00172.

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Abstract Appropriate thyroid hormone (TH) signaling through thyroid hormone receptors (TRs) is essential for vertebrate development. Amphibian metamorphosis is initiated and sustained through the action of TH on TRs, which are conserved across vertebrates. TRs heterodimerize with retinoid X receptors (RXRs) on thyroid hormone response elements (TREs) in the genome; however, in most cell line and adult animal studies, RXR ligands do not affect expression of TR target genes. We used a quantitative, precocious metamorphosis assay to interrogate the effects of the RXR agonist bexarotene (Bex) and the RXR antagonist UVI 3003 (UVI) on T3-induced resorption phenotypes in Xenopus laevis tadpoles 1 week postfertilization. Bex potentiated gill and tail resorption, and UVI abrogated T3 action. These results held in transgenic tadpoles bearing a TRE-driven luciferase reporter. Therefore, we used poly-A-primed RNA sequencing transcriptomic analysis to determine their effects on T3-induced gene expression. We also assayed the environmental pollutant tributyltin (TBT), which is an RXR agonist. We found that the proteases that carry out resorption were potentiated by Bex and TBT but were not significantly inhibited by UVI. However, several transcription factors from multiple families (sox4, fosl2, mxd1, mafb, nfib) were all inhibited by UVI and potentiated by Bex and TBT. All required T3 for induction. Time course analysis of gene expression showed that although the agonists could potentiate within 12 hours, the antagonist response lagged. These data indicate that the agonists and antagonist are not necessarily functioning through the same mechanism and suggest that RXR liganding may modulate TH competence in metamorphic signaling.
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17

Babalola, Oluwaseun O., J. Christoff Truter, and Johannes H. van Wyk. "Impacts of three glyphosate formulations on gonadal development of Xenopus laevis." Toxicology Research and Application 5 (January 2021): 239784732110314. http://dx.doi.org/10.1177/23978473211031467.

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The emergence of widespread morphological malformations in the reproductive system of wildlife is generating increasing concerns. This concern is because the observed malformities may be linked to pollution by pesticides and other chemicals. The amphibian declines, for example, have been linked to pesticide pollution among other factors. Using an extended Xenopus Metamorphosis Assay protocol, until the tadpoles metamorphosized, the exposure impacts of three glyphosate formulations, namely, Roundup, Kilo Max and Enviro Glyphosate, were assessed on the reproductive system of Xenopus laevis, vis-a-vis the body mass, sex ratios and morphological malformations as endpoints. The exposure concentrations ranged between 0.2–0.6 mg/L, 0.9–28 mg/L and 90–280 mg/L for Roundup, Enviro Glyphosate, and Kilo Max, respectively. Both Kilo Max and Enviro Glyphosate formulations significantly reduced the body mass of the metamorphs compared to the control. In sex ratios, only Kilo Max altered the percentage sex ratio of the treated frogs at a ratio of 68:32 (F:M) compared to 50:50 ratio in the control. In reproductive malformations, the three formulations showed abnormality index range of 22.3–49%, 17.5–37.5% and 20–30% for the Kilo Max, Enviro Glyphosate and Roundup formulations, respectively, compared to 7.5% in the control. Observed reproductive malformations include mixed sex, translucence, aplasia, segmented hypertrophy and segmented aplasia and translucence. This result indicates that some of the glyphosate formulations have the capacity to cause widespread reproductive malformations in a way that could reduce the reproductive fitness of the amphibian. Care must therefore be taken to reduce the application rate of these formulations, particularly in aquatic environments.
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18

Saka, Masahiro, Noriko Tada, and Yoichi Kamata. "Application of an amphibian (Silurana tropicalis) metamorphosis assay to the testing of the chronic toxicity of three rice paddy herbicides: Simetryn, mefenacet, and thiobencarb." Ecotoxicology and Environmental Safety 92 (June 2013): 135–43. http://dx.doi.org/10.1016/j.ecoenv.2013.03.023.

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19

Haselman, Jonathan T., Jennifer H. Olker, Patricia A. Kosian, Joseph J. Korte, Joseph A. Swintek, Jeffrey S. Denny, John W. Nichols, Joseph E. Tietge, Michael W. Hornung, and Sigmund J. Degitz. "Targeted Pathway-based In Vivo Testing Using Thyroperoxidase Inhibition to Evaluate Plasma Thyroxine as a Surrogate Metric of Metamorphic Success in Model Amphibian Xenopus laevis." Toxicological Sciences 175, no. 2 (March 16, 2020): 236–50. http://dx.doi.org/10.1093/toxsci/kfaa036.

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Abstract Chemical safety evaluation is in the midst of a transition from traditional whole-animal toxicity testing to molecular pathway-based in vitro assays and in silico modeling. However, to facilitate the shift in reliance on apical effects for risk assessment to predictive surrogate metrics having characterized linkages to chemical mechanisms of action, targeted in vivo testing is necessary to establish these predictive relationships. In this study, we demonstrate a means to predict thyroid-related metamorphic success in the model amphibian Xenopus laevis using relevant biochemical measurements during early prometamorphosis. The adverse outcome pathway for thyroperoxidase inhibition leading to altered amphibian metamorphosis was used to inform a pathway-based in vivo study design that generated response-response relationships. These causal relationships were used to develop Bayesian probabilistic network models that mathematically determine conditional dependencies between biochemical nodes and support the predictive capability of the biochemical profiles. Plasma thyroxine concentrations were the most predictive of metamorphic success with improved predictivity when thyroid gland sodium-iodide symporter gene expression levels (a compensatory response) were used in conjunction with plasma thyroxine as an additional regressor. Although thyroid-mediated amphibian metamorphosis has been studied for decades, this is the first time a predictive relationship has been characterized between plasma thyroxine and metamorphic success. Linking these types of biochemical surrogate metrics to apical outcomes is vital to facilitate the transition to the new paradigm of chemical safety assessments.
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20

Rabelo, Elida M. L., and Jamshed R. Tata. "Prolactin inhibits auto- and cross-induction of thyroid hormone and estrogen receptor and vitellogenin genes in adult Xenopus (Amphibia) hepatocytes." Brazilian Journal of Genetics 20, no. 4 (December 1997): 619–24. http://dx.doi.org/10.1590/s0100-84551997000400010.

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It is well known that virtually every tissue of the amphibian larvae is highly sensitive to the mutually antagonistic actions of thyroid hormone (TH) and prolactin (PRL), but it is not known if adult amphibian tissues respond similarly to these two hormones. We have previously shown that very low doses of triiodothyronine (T3) rapidly and strongly potentiate the activation of silent vitellogenin (Vit) genes by estrogen (E2) and the autoinduction of estrogen receptor (ER) transcripts in primary cultures of adult Xenopus hepatocytes. This response to T3 is accompanied by the upregulation of thyroid hormone receptor <FONT FACE="Symbol">b</FONT> (TR<FONT FACE="Symbol">b</FONT>) mRNA. Using Northern blot and RNase protection assays, we now show that ovine PRL added for 12 h along with 2 x 10-9 M T3 will completely prevent potentiation of E2 induction of Vit mRNA in primary cultures of adult Xenopus hepatocytes. PRL also abolished the auto-upregulation of TR<FONT FACE="Symbol">b</FONT> mRNA and the cross-activation of autoinduction of ER mRNA. Thus, we show for the first time that the anti-TH action of PRL that is manifested in Xenopus tadpole tissues during metamorphosis is retained in adult liver, and suggest that the mutually antagonistic actions of the two hormones may be brought about by similar molecular mechanisms in larval and adult amphibian tissues
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21

Zhang, Yin-Feng, Hai-Ming Xu, Fei Yu, Hong-Yu Yang, Dong-Dong Jia, and Pei-Feng Li. "Comparison the sensitivity of amphibian metamorphosis assays with NF 48 stage and NF 51 stage Xenopus laevis tadpoles." Toxicology Mechanisms and Methods 29, no. 6 (March 20, 2019): 421–27. http://dx.doi.org/10.1080/15376516.2019.1579291.

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22

Kawahara, A., B. S. Baker, and J. R. Tata. "Developmental and regional expression of thyroid hormone receptor genes during Xenopus metamorphosis." Development 112, no. 4 (August 1, 1991): 933–43. http://dx.doi.org/10.1242/dev.112.4.933.

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A characteristic feature of the obligatory control of amphibian metamorphosis by thyroid hormones is the early acquisition of response of tadpole tissues to these hormones well before the latter are secreted, with ‘exponentially’ increasing hormonal sensitivity upon the onset of metamorphosis. We have therefore analyzed the expression of the two thyroid hormone receptor genes (TR alpha and beta) before, during and after metamorphosis in Xenopus tadpoles and froglets. Using non-cross-hybridizing cRNA probes for 5′ and 3′ sequences of Xenopus TR alpha and beta transcripts for RNAase protection assays, the two mRNAs can be detected in tadpoles as early as stage 39. Their concentration increases abruptly at stage 44 and continues to increase differentially at the onset of metamorphosis (stage 55) and through metamorphic climax at stages 58–62, after which they decline upon completion of metamorphosis at stage 66. Quantitative densitometric scanning of autoradiograms showed that, although the concentration of TR beta transcripts is about 1/30th of that of TR alpha mRNA at stages 44–48, depending on the region, it accumulates 3–10 times more rapidly than does the alpha isoform during further development. A substantial proportion of the increase in TR beta mRNA is localized to the head region of tadpoles. Using the hormone-binding domain (HBD) and 3′ end of Xenopus TR alpha cRNA as probe for in situ hybridization, the highest concentration of TR transcripts in stage 44 tadpoles is seen in the brain and spinal cord. High concentrations of mRNA are also present in the intestinal epithelium and tail tip, tissues programmed for regression. At later stages (55 onwards), strong hybridization signals are also exhibited by hindlimb buds. This pattern persists through metamorphic climax, after which TR mRNAs decline in all tissues to low levels in froglets at stage 66. In developing froglets, TR transcripts were detected in large amounts in the cytoplasm of stage 1 and 2 oocytes but the rate of their accumulation did not increase with further oocyte growth. This observation raises the possibility that the response to thyroid hormones at early stages of tadpoles (42–44) may be due to TR synthesized on maternally derived mRNA. Exposure of tadpoles at premetamorphic stages (48–52) to exogenous thyroid hormone (T3) substantially enhanced the accumulation of TR mRNA, especially that of TR beta message, which could explain the accelerated increase in sensitivity of tadpoles to thyroid hormones at the onset of natural metamorphosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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