Effects of multiple life stage exposure to the fungicide prochloraz in Xenopus laevis: Manifestations of antiandrogenic and other modes of toxicity
| Autor: | Joseph J. Korte, Jonathan T. Haselman, Patricia A. Kosian, Sigmund J. Degitz, Allen W. Olmstead |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Amphibian Health Toxicology and Mutagenesis Xenopus 010501 environmental sciences Aquatic Science Pharmacology 01 natural sciences Article Vitellogenins Xenopus laevis 03 medical and health sciences biology.animal Toxicity Tests medicine Animals Mode of action Testosterone 0105 earth and related environmental sciences Life Cycle Stages biology Leydig cell Imidazoles Gene Expression Regulation Developmental Androgen Antagonists biology.organism_classification Prochloraz Fungicides Industrial Fungicide 030104 developmental biology medicine.anatomical_structure Organ Specificity Toxicity Female Water Pollutants Chemical |
| Zdroj: | Aquatic Toxicology. 199:240-251 |
| ISSN: | 0166-445X |
| Popis: | The Larval Amphibian Growth and Development Assay (LAGDA) is an internationally harmonized testing guideline for evaluating effects of chronic chemical exposure in amphibians. In order to evaluate the effects of chronic exposure to an antiandrogenic chemical in an amphibian model, prochloraz was tested using a variation of the LAGDA design. Exposure was initiated with < 1d post-fertilization embryos at nominal concentrations of 0, 6.7, 20, 60 and 180 μg/L (0, 18, 53, 159, 478 nM) and continued in flow-through conditions until two months following the median time that controls completed metamorphosis. Growth, developmental rate, circulating thyroid hormone and thyroid gland histopathology were evaluated in a subsample at completion of metamorphosis. There were no effects on growth or development at this stage, but circulating thyroid hormone was elevated in the 20, 60 and 180 μg/L treatments and minimal to mild thyroid follicular cell hypertrophy was observed histologically in the 180 μg/L treatment. Growth, overt toxicity, and reproductive development were evaluated at test termination. There were no effects on growth in either gender, but livers and kidneys exhibited treatment-related pathologies consistent with organ toxicity related to metabolism and presumably impaired excretion of prochloraz metabolites. Histological assessments of female ovaries resulted in minimal pathologies only in the 180 μg/L treatment while male testes exhibited numerous treatment-related pathologies that are consistent with previously reported antiandrogenic effects of prochloraz in other species. The most severe testis pathologies occurred in the 180 μg/L treatment; however, incidences of treatment-related pathologies occurred in all prochloraz treatments. Müllerian duct involution in males was inhibited by prochloraz exposure while Müllerian duct maturation in females was accelerated, characteristic of a feminizing effect. Gene expression levels of potential biomarkers of testis function were also measured. Relative abundance of cyp17a1 transcripts was generally unaffected by prochloraz exposure whereas the Insl3 orthologue, rflcii, was elevated by 3 and >5-fold in the 60 and 180 μg/L treatments, respectively indicating an adaptive response to increase Leydig cell differentiation and ultimately increase testosterone production. Overall, prochloraz exposure caused effects characteristic of an antiandrogenic mode of action, which is consistent with previously reported results in other species and supports the utility of the LAGDA design for chemical testing. |
| Databáze: | OpenAIRE |
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