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Background
Okadaic acid (OA) is an important liposoluble shellfish toxin distributed worldwide, and mainly responsible for diarrheic shellfish poisoning (DSP) in human beings. It has a variety of toxicities, including cytotoxicity, embryonic toxicity, neurotoxicity, and even genotoxicity. The embryotoxicity of OA is due to it can cross the placental barrier, which was proven in mice. However, there is no direct evidence of its developmental toxicity in human offspring. The chicken (Gallus gallus) embryo is a classic animal model for the studies of early vertebrate embryogenesis and late organogenesis due to its multiple advantages, such as convenience for observation, similarity to mammalian embryo, easy accessibility, and manipulation, etc.
Results
OA exposure could cause NTDs and inhibit the neuronal differentiation. Immunofluorescent staining demonstrated that OA exposure promoted cell proliferation and inhibit cell apoptosis on the developing neural tube. Besides, the down-regulation of Nrf2 and increases in ROS content and SOD activity in the OA-exposed chicken embryos indicated that OA could result in the generation of oxidative stress in early chick embryos. The inhibition of BMP4 and Shh expression in the dorsal neural tube suggested that OA could also affect the formation of dorsolateral hinge points. The expression of LBP, JUN, FOS, and CCL4 in Toll-like receptor signaling pathway was significantly increased in the OA-exposed embryos, suggesting that the NTDs induced by OA might be associated with Toll-like receptor signaling pathway.
Conclusion
OA exposure can induce NTDs in chick embryos and increase the incidences of embryo mortality and malformation. Oxidative stress in early chick embryos may be subsequently responsible for the formation of NTDs. OA exposure can affect cell proliferation and apoptosis. Toll-like receptor signaling pathway may be responsible for the NTDs induced by OA.
Keywords
Okadaic acid, Chick embryo model, NTDs, Tolk-like signaling pathway
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 18 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Okadaic acid (OA) is an important liposoluble shellfish toxin distributed worldwide, and mainly responsible for diarrheic shellfish poisoning (DSP) in human beings. It has a variety of toxicities, including cytotoxicity, embryonic toxicity, neurotoxicity, and even genotoxicity. The embryotoxicity of OA is due to it can cross the placental barrier, which was proven in mice. However, there is no direct evidence of its developmental toxicity in human offspring. The chicken (Gallus gallus) embryo is a classic animal model for the studies of early vertebrate embryogenesis and late organogenesis due to its multiple advantages, such as convenience for observation, similarity to mammalian embryo, easy accessibility, and manipulation, etc.
Results
OA exposure could cause NTDs and inhibit the neuronal differentiation. Immunofluorescent staining demonstrated that OA exposure promoted cell proliferation and inhibit cell apoptosis on the developing neural tube. Besides, the down-regulation of Nrf2 and increases in ROS content and SOD activity in the OA-exposed chicken embryos indicated that OA could result in the generation of oxidative stress in early chick embryos. The inhibition of BMP4 and Shh expression in the dorsal neural tube suggested that OA could also affect the formation of dorsolateral hinge points. The expression of LBP, JUN, FOS, and CCL4 in Toll-like receptor signaling pathway was significantly increased in the OA-exposed embryos, suggesting that the NTDs induced by OA might be associated with Toll-like receptor signaling pathway.
Conclusion
OA exposure can induce NTDs in chick embryos and increase the incidences of embryo mortality and malformation. Oxidative stress in early chick embryos may be subsequently responsible for the formation of NTDs. OA exposure can affect cell proliferation and apoptosis. Toll-like receptor signaling pathway may be responsible for the NTDs induced by OA.
Figure 1
Figure 1
Figure 1
Figure 1
Figure 1
Figure 1
Figure 1
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
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