Background: Widely utilized pesticides such as chlorpyrifos (CPF) can cause cognitive abnormalities, neurotransmitter disruptions and brain cytoarchitecture deficits in adulthood due to exposure in the prenatal period, but the mechanism underlying the development and maintenance of such neurotoxicity in embryonic neurogenesis remains largely unclear. Using embryonic neocortex slices, we investigated mitosis population constituents and characteristic interkinetic nuclear migration (INM) to evaluate the CPF effects on the proliferation process of neural progenitors. Methods: Gestational days (GD) 14 and GD 7.5-11.5 ICR dams were exposed to 5 mg kg-1 of CPF to investigate immediate toxicity and sustained toxicity. Proliferating nuclei were labeled with 50 mg kg-1 of Brdu at 1, 3, 6 and 9 hours before samples were collected. The mitoses count and Brdu positive nuclei (BPN) location were measured and analyzed in standard sections of the embryonic dorsolateral cortex. Results: CPF reduced the mitoses count in the primary progenitors but not in the secondary progenitors which are time sustained. CPF retarded BPN migration with a 6-9 μm delay of the relative location in the immediate groups and a 3-6 μm delay in the sustained ones. CPF had no or little effects on the global mitoses count and BPN count. Conclusion: Prenatal CPF exposure disrupts the proliferation process of primary progenitors in the embryonic dorsolateral cortex immediately and with sustained effects, which may contribute to explain the toxicity mechanism in early neurogenesis.

中文翻译：

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一项小鼠体内研究：母亲在妊娠期接触有机磷农药会延迟胎儿发育大脑中神经祖细胞的分裂和迁移过程。


背景：广泛使用的农药，如毒死蜱（CPF），由于在产前时期接触，可导致成年期认知异常、神经递质破坏和脑细胞结构缺陷，但胚胎神经发生中这种神经毒性的发展和维持的机制仍不清楚。使用胚胎新皮质切片，我们研究了有丝分裂群体成分和特征性互动核迁移（INM），以评估 CPF 对神经祖细胞增殖过程的影响。方法：妊娠第 14 天和 GD 7.5-11.5 个 ICR 母鼠暴露于 5 mg kg-1 的 CPF，以研究立即毒性和持续毒性。收集样品前 1、3、6 和 9 小时用 50 mg kg-1 Brdu 标记增殖细胞核。在胚胎背外侧皮层的标准切片中测量和分析有丝分裂计数和 Brdu 阳性核 (BPN) 位置。结果：CPF 减少了初级祖细胞中的有丝分裂计数，但不减少了次要祖细胞中持续时间的有丝分裂计数。 CPF 延迟了 BPN 迁移，直接组中的相对位置延迟了 6-9 μm，持续组中的相对位置延迟了 3-6 μm。 CPF 对整体有丝分裂计数和 BPN 计数没有影响或影响很小。结论：产前CPF暴露立即扰乱胚胎背外侧皮层初级祖细胞的增殖过程，并产生持续影响，这可能有助于解释早期神经发生的毒性机制。