Role Of Nrf2 Mediated Antioxidant Defense Response In Cadmium-induced Heteroplasia Of Neural Tubes In Chick Embryos

Cadmium is one of the strongest contaminants in the environment.Ultimately,the concentration of cadmium is increasing with the accumulation of food chain,causing sorts of organ and tissue damage.Numerous studies have shown that cadmium can pass the placentato influencing the development of nervous system in embryos.However,it is still poorly understood in the mechanism of cadmium to the development of neural tube in embryos.In this study,chick embryos were used as cadmium exposure model.Cadmium was injected into the yolk of the chick embryos in HH-4,then morphological alterations in chick embryos and the neural tubes were observed in HH-12.Additionally,anti-oxidative function and role of Nrf2-mediated antioxidant defense response in HH-12 chick embryos were detected.The results showed that:The mortality risk was increased in chick embryos,embryonic development time was prolonged and the malformation rate was increased in cadmium-exposured chick embryos.The results showed that cadmium can cause developmental lag and malformation in chick embryos,which revealing that cadmium had significant toxicity on the development of chick embryos.Cadmium could cause the increase of m RNA level in Shh and the decrease of mRNA level in Pax3 and Pax7.Additionally,with the increase of cadmium concentration,the defect rate of neural tube in chick embryos was increased.The results indicated that cadmium can cause the neural tubes defects in chick embryos.The contents of MDA and H₂O₂ were increased,however,the activities of SOD,CAT,GSH-Px and the content of GSH were decreased significantly.Additionally,cadmium exposure decreased the level of T-AOC in the chick embryos.The results indicated that cadmium can increase free radical and lipid peroxide levels,decrease antioxidant enzymes activities,and disrupt the antioxidant defense system in chick embryos.Eventually,cadmium can introduce the oxidative stress,which may be one of the mechanisms on cadmium-introduced neural tube defects in early chick embryos.The m RNA levels of Nrf2 and phase II enzyme-related genes?NQO1,HO-1,CAT,GST,GCLC,GCLM,SOD1-3?in chick embryos were increased by the exposure of low concentration cadmium.However,the mRNA level of these factors above were inhibited by the exposure of high concentration cadmium.The results showed that Nrf2-mediated antioxidant defense response candefend oxidative stress induced by cadmium,which indicated Nrf2-mediated antioxidant defense response can play a protective role in cadmium-induced neural tubes defects in chick embryos.