The thyroid-disrupting effects of long-term perfluorononanoate exposure on zebrafish (Danio rerio)

Concentrations of perfluorononanoate (PFNA) suggest an obvious increase in the environment, wildlife, and humans. However, the potential toxicity of PFNA still remains to be fully elucidated. Our present work is directed toward evaluating specific thyroid endpoints, and studying the long-term and the trans-generational effects of PFNA on zebrafish. Zebrafish (Danio rerio) were exposed to different concentrations of PFNA (0, 0.05, 0.1, 0.5, and 1 mg/l) from their early life stages (F0, 23 day post-fertilization dpf), and the exposure period lasted for 180 days. At the end of the exposure period, thyroid follicle histology and plasma thyroid hormone levels in male zebrafish were evaluated as direct endpoints for the specific thyroid toxicities, while gene expression relative to the hypothalamus–pituitary–thyroid axis was also investigated to study the underlying mechanisms. In addition, offspring embryos (F1) from the PFNA exposure parental zebrafish was reared in water either without PFNA or under continual exposure to PFNA for an additional 180 days to investigate effects of multi-generational exposures on the circulating T3 levels and thyroid-associated gene expression. Our results demonstrate significantly elevated plasma T3 levels were observed in both F0 and F1 adults, as well as PFNA-induced histological changes in the thyroid follicles of F0 male zebrafish. In the liver, the abundance of gene transcript encoding the protein transthyretin (TTR) was significantly induced, while the expression of UDP-glucuronosyltransferases in F0 adult males was inhibited. The induced thyroid-disrupting effects also demonstrated a trans-generational effect that was reflected by altered gene expression related to thyroid hormone (TH) synthesis and metabolism in F1 larvae. Our results provide the first evidence for the thyroid-disrupting effects of long-term PFNA exposure in zebrafish.