Abstract
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.
Okadaic acid exposure induced neural tube defects in chicken (Gallus gallus) embryos
