PUBLICATION
Bioaccumulation and thyroid endcrione disruption of 2-ethylhexyl diphenyl phosphate at environmental concentration in zebrafish larvae
- Authors
- Shu, Y., Yuan, J., Hogstrand, C., Xue, Z., Wang, X., Liu, C., Li, T., Li, D., Yu, L.
- ID
- ZDB-PUB-240108-1
- Date
- 2023
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 267: 106815106815 (Journal)
- Registered Authors
- Keywords
- EHDPP, Environmental concentration, In vivo toxicity, TTR protein, Thyroid hormone, Zebrafish
- MeSH Terms
-
- Animals
- Bioaccumulation
- Biphenyl Compounds*
- Endocrine Disruptors*/metabolism
- Endocrine Disruptors*/toxicity
- Larva
- Molecular Docking Simulation
- Phosphates/metabolism
- Prealbumin/genetics
- Prealbumin/metabolism
- Prealbumin/pharmacology
- Thyroid Gland
- Thyroid Hormones/metabolism
- Water Pollutants, Chemical*/toxicity
- Zebrafish/metabolism
- PubMed
- 38185038 Full text @ Aquat. Toxicol.
Citation
Shu, Y., Yuan, J., Hogstrand, C., Xue, Z., Wang, X., Liu, C., Li, T., Li, D., Yu, L. (2023) Bioaccumulation and thyroid endcrione disruption of 2-ethylhexyl diphenyl phosphate at environmental concentration in zebrafish larvae. Aquatic toxicology (Amsterdam, Netherlands). 267:106815106815.
Abstract
2-ethylhexyl diphenyl phosphate (EHDPP) strongly binds to transthyretin (TTR) and affects the expression of genes involved in the thyroid hormone (TH) pathway in vitro. However, it is still unknown whether EHDPP induces endocrine disruption of THs in vivo. In this study, zebrafish (Danio rerio) embryos (< 2 h post-fertilization (hpf)) were exposed to environmentally relevant concentrations of EHDPP (0, 0.1, 1, 10, and 100 μg·L-1) for 120 h. EHDPP was detected in 120 hpf larvae at concentrations of 0.06, 0.15, 3.71, and 59.77 μg·g-1 dry weight in the 0.1, 1, 10, and 100 μg·L-1 exposure groups, respectively. Zebrafish development and growth were inhibited by EHDPP, as indicated by the increased malformation rate, decreased survival rate, and shortened body length. Exposure to lower concentrations of EHDPP (0.1 and 1 μg·L-1) significantly decreased the whole-body thyroxine (T4) and triiodothyronine (T3) levels and altered the expressions of genes and proteins involved in the hypothalamic-pituitary-thyroid axis. Downregulation of genes related to TH synthesis (nis and tg) and TH metabolism (dio1 and dio2) may be partially responsible for the decreased T4 and T3 levels, respectively. EHDPP exposure also significantly increased the transcription of genes involved in thyroid development (nkx2.1 and pax8), which may stimulate the growth of thyroid primordium to compensate for hypothyroidism. Moreover, EHDPP exposure significantly decreased the gene and protein expression of the transport protein transthyretin (TTR) in a concentration-dependent manner, suggesting a significant inhibitory effect of EHDPP on TTR. Molecular docking results showed that EHDPP and T4 partly share the same mode of action of binding to the TTR protein, which might result in decreased T4 transport due to the binding of EHDPP to the TTR protein. Taken together, our findings indicate that EHDPP can cause TH disruption in zebrafish and help elucidate the mechanisms underlying EHDPP toxicity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping