Effects of the antithyroid agent propylthiouracil in a partial life cycle assay with zebrafish.
Some ubiquitous pollutants of the aquatic environment, such as PCBs or other polyhalogenated aromatic hydrocarbons, may disrupt the thyroid hormone system. In a partial life cycle assay with zebrafish (Danio rerio), we studied the effects of the reference compound propylthiouracil (PTU) on reproduction, growth and development, histopathology of some target tissues, and plasma thyroid hormone levels. PTU induced a concentration-dependent increase of egg production with a concomitant decrease of mature oocyte size but had no effect on fertilization rate or hatching. In F1, serious dysmorphogenesis was found in 4 dph larvae at the highest PTU level tested (100 mg/L), and there was a dose-dependent decrease in body length and weight at 42 dph (significant at 100 mg/L PTU). At this time, there was also a decreased scale thickness, suggesting inhibited metamorphosis, detectable at 1 mg/L PTU and higher. PTU also induced activation of the thyroid follicles in a concentration-dependent way, in juveniles associated with hyperemia in the thyroid area, and depletion of liver glycogen. Effects in adults were associated with decreased circulating levels of the thyroid hormones T3 and T4. These observations indicate that disruption of the thyroid hormone system may affect the fitness of these aquatic organisms. The zebrafish model may contribute to the identification of thyroid hormone disrupting activity in water samples and also in the interpretation of histological observations in free-ranging fish species.
van der Ven
Leo T M
LT
Laboratory for Toxicology, Pathology, and Genetics, RIVM, TOX 12, PO Box 1, NL-3720 BA Bilthoven, The Netherlands. L.van.der.ven@rivm.nl
van den Brandhof
Evert-Jan
EJ
Vos
José H
JH
Power
Deborah M
DM
Wester
Piet W
PW
D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity*; D001681:Biological Assay; D049628:Body Size / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006128:Growth / Q000187:drug effects; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D008018:Life Cycle Stages; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008112:Liver Glycogen / Q000097:blood; D011441:Propylthiouracil / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects* / Q000648:ultrastructure; D013963:Thyroid Hormones / Q000097:blood; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish
D013956:Antithyroid Agents; D008112:Liver Glycogen; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; D011441:Propylthiouracil