Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos.
Yuhu JiaoGuang WangDawei LiHong-Ye LiJiesheng LiuXuesong YangWeidong YangPublished in: Marine drugs (2021)
Okadaic acid (OA) is an important liposoluble shellfish toxin distributed worldwide, and is mainly responsible for diarrheic shellfish poisoning in human beings. It has a variety of toxicities, including cytotoxicity, embryonic toxicity, neurotoxicity, and even genotoxicity. However, there is no direct evidence of its developmental toxicity in human offspring. In this study, using the chicken (Gallus gallus) embryo as the animal model, we investigated the effects of OA exposure on neurogenesis and the incidence of neural tube defects (NTDs). We found that OA exposure could cause NTDs and inhibit the neuronal differentiation. Immunofluorescent staining of pHI3 and c-Caspase3 demonstrated that OA exposure could promote cell proliferation and inhibit cell apoptosis on the developing neural tube. Besides, the down-regulation of Nrf2 and increase in reactive oxygen species (ROS) content and superoxide dismutase (SOD) activity in the OA-exposed chicken embryos indicated that OA could result in oxidative stress in early chick embryos, which might enhance the risk of the subsequent NTDs. The inhibition of bone morphogenetic protein 4 (BMP4) and Sonic hedgehog (Shh) expression in the dorsal neural tube suggested that OA could also affect the formation of dorsolateral hinge points, which might ultimately hinder the closure of the neural tube. Transcriptome and qPCR analysis showed the expression of lipopolysaccharide-binding protein (LBP), transcription factor AP-1 (JUN), proto-oncogene protein c-fos (FOS), and C-C motif chemokine 4 (CCL4) in the Toll-like receptor signaling pathway was significantly increased in the OA-exposed embryos, suggesting that the NTDs induced by OA might be associated with the Toll-like receptor signaling pathway. Taken together, our findings could advance the understanding of the embryo-fetal developmental toxicity of OA on human gestation.
Keyphrases
- toll like receptor
- knee osteoarthritis
- oxidative stress
- binding protein
- endothelial cells
- signaling pathway
- inflammatory response
- reactive oxygen species
- cell proliferation
- nuclear factor
- immune response
- dna damage
- poor prognosis
- cell death
- induced apoptosis
- escherichia coli
- epithelial mesenchymal transition
- induced pluripotent stem cells
- spinal cord
- diabetic rats
- pluripotent stem cells
- nitric oxide
- ischemia reperfusion injury
- small molecule
- pregnant women
- gene expression
- risk factors
- high glucose
- metabolic syndrome
- subarachnoid hemorrhage
- preterm infants
- brain injury
- high fat diet
- working memory
- endoplasmic reticulum stress
- insulin resistance
- high speed
- heat shock
- drug induced