Effects Of Gestational Exposure To Organophosphate Pesticide Chlorpyrifos On Neural Precursor Cell Proliferation And Differentiation In Embryonic Mouse

Organophosphorus pesticides,especially chlorpyrifos,are widely used in agricultural production,which pose a serious threat on public health and the environment due to its long-term low-dose exposure to the environment.CPF was widespread concerned because of its potential neurotoxic.In vivo studies have found that neurodevelopmental sensitivity CPF exposure may cause changes in the brain regions structure and cause permanent damage to the offspring neurobehavioral.However,the mechanism of brain structure and neurobehavioral changes because exposure to CPF are also unclear.To further explore the neurodevelopmental toxicity mechanism of embryonic CPF exposure on offspring,we research the effect of embryonic exposure to CPF on the length of G2 / M phase of neural progenitor proliferation in subventricular zone and organizational structure of somatosensory cortex and lateral ventricle wall in embryonic mouse.Then,we study the effect of CPF on neural progenitor cell differentiation fate.We established pregnant mouse exposed model through exposure to sub-toxic doses of CPF in early neural development(E7.5-E11.5).In E14,pregnant mouse were single injected with 5-bromo-2'-deoxyuridine(Brdu)to label cells in S phase.Then,we count the number of Brdu+ cells and mitotic cells in VZ zone of lateral ventricle wall and calculate Brdu+ cell labeling index and the length of G2 / M phase to analyze the impact of CPFon embryonic neural precursor cells proliferating cell number and the cell cycle of proliferation through tissue sections and Brdu immunohistochemical staining embryo after marking 0.5 h,1.0 h,1.5 h,2.0h and 2.5 h.Then,dynamic observation was observed at different developmental stages with the same dose exposure to mouse embryos to study the effect of CPF on cell density of each region of lateral ventricle wall and somatosensory cortex.Finally,we discuss the impact of the CPF newborn neurons fate of E14 lateral ventricle by Tbr1 immunohistochemical staining.The results show that CPF exposure during early pregnancy reduced the number of cells in S phase in embryos lateral ventricle wall and delayed the length of G2 and M phases of neural precursor cells in VZ zone by17.3% and 50.3%.We also found that,in E12 lateral ventricle wall,CPF lead to a reduction of 21.8% on the number of proliferative zone(VZ)cells,and an increase of 63.9% on the number of differentiated zone(PP)cells.In E14,CPF caused the number of proliferative zone(VZ and SVZ)cells reduced by 22.2%,but the differentiation zone(IZ and CP)no significant change.Study on somatosensory cortex,we found no significant effect on cell number and cell density in E14,however,the number of cells and cell density were reduced by 13.3%(E16)and 19.2%(E18).The cytostatic was enhanced along with the continuation of the development.At the same time,we found CPF reduced by 8.8% on the number of Tbr1+ neurons.In conclusion,early embryo exposure to sub-toxic doses CPF delayed neural precursor cell proliferation cycle and lead to cortical development disorders.