Effects Of Prenatal Exposure To Low-Dose Chlorpyrifos On The Morphology With Lateral Ventricle In Embryonic Mouse

Chlorpyrifos (CPF) can cause neurotoxicity in the embryonic development. It was shown that CPF directly affect the developmental fate of PC12cells in procession from proliferation to differentiation. In vivo studies, CPF exposure at embryonic and neonatal stages elicited brain neurotransmitter disorders, cognitive abnormalities and brain structural damages. However, the working mechanism is still unclear. In this study, we focused at a new investigation angle, the apical-basal polarity of the lateral ventricle, to evaluate the effects of prenatal CPF exposure on proliferation/differentiation pool of developmental neocortex, and the long-term effects of prenatal CPF on ACd of mPFC.We first given5mg/kg/d CPF injection to E7.5-11.5ICR mice and obtained the embryo brains at E12, E14and E16. Sections of the lateral ventricles were made and HE staining was performed. The thickness of different layers in the lateral ventricular wall were measured. Secondly, immunohistochemical staining with TUJ1(the neuron marker) and pax6(the progenitor marker) was performed in E14brain sections and the positive cell number was counted to evaluate the effects of prenatal CPF to the neural progenitors and neurons. Finally, Nissel’s staining was performed and the cytoarchitecture was observed in ACd of mPFC of PND60mice after E13-16CPF exposure.The results showed that CPF pretreatment induced a thiner proliferation pool and a thicker differentiation pool, especially at E16brain. Immunohistochemical staining results showed a decreased cell number count in neural progenitors but no change in the number of neurons at E14brain. CPF prenatal exposure reduced the total cell number, neuron number, and glial number in adult ACd of mPFC, with no obvious morphological abnormals in these cells. In conclusion, these results confirmed our previous hypothesis, that CPF may cause developmental neurotoxicity by breaking the balance of the proliferation and differentiation in neurogeonesis. Moreover, our reults proved that CPF embryonic exposure leave a long time damage at adult mice brain ACd region.