| Exposure to organophosphorus pesticide(OPs)diazinon(DZN)at a low concentration will affect the embryonic neural development,leading to abnormal cognitive behaviors and emotional reactions,and the specific mechanisms of DZN developmental toxicity need further study.In this research,we study the effect of DZN on apical progenitor cells(APs)from the perspective of Interkinetic nuclear migration(INM),analysis the abnormal outcome of proliferation and differentiation,and evaluate the persistence of this effect.In chapter 2,we given 0,1,5mg / kg DZN to GD14 ICR mice for three consecutive times in 3 hour intervals,measured AChE activity of maternal blood and embryos,Caspase-3 activity and SOD activity of embryos,to analysis the acute toxicity of DZN on brain tissue and the recovery.The results show that 5mg / kg DZN caused cholinesterase activity of E14,E16,E18 maternal blood decreased to 40.25%,60.34%,80.32% compared to the normal value;The cholinesterase activity of E14,E16 embryonic brain decreased to 62.53%和 79.41% to the normal value,and closed to normal value in E18;The Caspase-3 activity of E14,E16 embryonic brain increased to 148.64% and 113.86% respectively,and also closed to normal value in E18;SOD activity in three time points showed no significant change.In chapter 3,we given Brdu injection to the DZN exposed mice to mark cells in S-phase,prepared Brdu-labeled 1h,3h,6h embryos,and performed Brdu immunohistochemical staining,to study the effect of DZN on division and proliferation of Aps.The results showed that the average position of Brdu+ at 1h and 3h has no significant changes compared with control after 1mg/kg DZN exposure,and the average position of Brdu+ at 6h was slightly delyed compared to the control after 1mg/kg DZN exposure;after 5mg/kg DZN exposure,the average position of Brdu+ at 1h,3h,6h in lateral ventricle was all significantly delyed compared to the control,DZN exposure significantly slowed the INM of Brdu+.In chapter 4,the DZN exposed embryos was performed Pax6,Tbr2,Tbr1 immunohistochemical staining to analysis the effect of DZN on the development of Aps.Statistics showed that 5mg / kg DZN significantly reduced Pax6 positive cells in vertricular zone(VZ)in E14、E16、E18,but not influence the positive cell number of Tbr2 and Tbr1,indicating that DZN exposure mainly affect APs which mainly exist in the early developmental stage,but not affect BPs and neurons.Conclusively,embryonic exposure to DZN will delay the process of division of APs,disrupt the balance of proliferation and differentiation of APs,reduce the proliferating cell population,and this effect will lasts longer even thouth acute enzyme activity has recovered... |
