Effects of lipophilic phycotoxin okadaic acid on the early development and transcriptional expression of marine medaka Oryzias melastigma

The lipophilic okadaic acid (OA)-group toxins produced by some species of Dinophysis spp. and Prorocentrum spp. marine dinoflagellates have been frequently and widely detected in natural seawater environments, e.g. 2.1-1780 ng/L in Spanish sea and 5.63-27.29 ng/L in the Yellow Sea of China. The toxicological effects of these toxins dissolved in seawater on marine fish is still unclear. Effects of OA on the embryonic development and 1 -month old larvae of marine medaka (Oryzias melastigma) were explored and discussed in this study. Significantly increased mortality and decreased hatching rates occurred for the medaka embryos exposed to OA at 1.0 mu g/mL. Diverse malformations including spinal curvature, dysplasia and tail curvature were also observed in the em-bryos exposed to OA and the heart rates significantly increased at 11 d post fertilization. The 96 h LC50 of OA for 1-month old larvae was calculated at 3.80 mu g/mL. The reactive oxygen species (ROS) was significantly accu-mulated in medaka larvae. Catalase (CAT) enzyme activity was significantly increased in 1-month old larvae. Acetylcholinesterase (AChE) activity significantly increased with a dose-dependent pattern in 1-month old larvae. Differentially expressed genes (DEGs) were enriched in 11 KEGG pathways with Q value < 0.05 in 1 -month old medaka larvae exposed to OA at 0.38 mu g/mL for 96 h, which were mainly related to cell division and proliferation, and nervous system. Most of DEGs involved in DNA replication, cell cycle, nucleotide excision repair, oocyte meiosis, and mismatch repair pathways were significantly up-regulated, while most of DEGs involved in synaptic vesicle cycle, glutamatergic synapse, and long-term potentiation pathways were markedly down-regulated. This transcriptome analysis demonstrated that a risk of cancer developing was possibly caused by OA due to DNA damage in marine medaka larvae. In addition, the neurotoxicity of OA was also testified for marine fish, which potentially cause major depressive disorder (MDD) via the up-regulated expression of NOS1 gene. The genotoxicity and neurotoxicity of OA to marine fish should be paid attention to and explored further in the future.

Automated summary

The study explored the toxicological effects of lipophilic okadaic acid (OA)-group toxins on marine fish and found increased mortality, decreased hatching rates, and various malformations in marine medaka embryos exposed to OA. It also identified significant accumulation of reactive oxygen species, increased CAT enzyme activity, and dose-dependent increase in AChE activity in 1-month old medaka larvae exposed to OA. Transcriptome analysis revealed potential DNA damage and cancer risk caused by OA, as well as neurotoxicity and risk of major depressive disorder. Further research on genotoxicity and neurotoxicity of OA to marine fish is needed.