Zhang Nan, Bo Nan, Wang Yuanhao, Bai Wenlin, Sun Wen, Zhao Zhenlin, Zhang Yuanbao, Zhang Yingying, Lei Lijian, Zhou Jianjun, Zhang Wenping
Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, China.
Department of Children and Adolescences Health, School of Public Health, Taiyuan, China.
Front Behav Neurosci. 2025 Apr 24;19:1571122. doi: 10.3389/fnbeh.2025.1571122. eCollection 2025.
Mid-gestation is a critical period for the development of the nervous system. Exposure to exogenous harmful chemicals during this period may lead to longterm neurological developmental abnormalities in offspring. Benzo[a]pyrene (B[a]P) is a commonly occurring neurotoxic environmental pollutant that can pass through the placental barrier and blood-brain barrier (BBB), thereby affecting placental nerve development.
To investigate the neurotoxic mechanism of B[a]P on offspring exposed in mid-gestation, pregnant rats were exposed to B[a]P (25 mg/kg) from gestation days 8 to 14. Meanwhile, as an agonist of Wnt/β-catenin signaling pathway, lithium chloride (LiCl) was administered to observe the intervention effects.
The results showed that in rats exposed to B[a]P in mid-gestation, the developmental nodes of the offspring were delayed, and the neurosensory sensitivity of the offspring was reduced. These offspring also had cognitive impairments in adulthood. Subsequent morphological and protein experiments showed that the exposed offspring had reduced neuronal complexity in the CA1 region of the hippocampus, decreased β-catenin expression, and increased GSK-3β expression in the hippocampal tissue. However, all these indexes can be reversed by LiCl.
These results suggest that B[a]P exposed in mid-gestation pregnancy may lead to neurological damage in the offspring by downregulating the Wnt/β-catenin signaling pathway.
妊娠中期是神经系统发育的关键时期。在此期间接触外源性有害化学物质可能会导致后代出现长期神经发育异常。苯并[a]芘（B[a]P）是一种常见的具有神经毒性的环境污染物，它可以穿过胎盘屏障和血脑屏障（BBB），从而影响胎盘神经发育。
为了研究妊娠中期暴露于B[a]P对后代的神经毒性机制，将怀孕大鼠在妊娠第8天至第14天暴露于B[a]P（25mg/kg）。同时，给予氯化锂（LiCl）作为Wnt/β-连环蛋白信号通路的激动剂，以观察其干预效果。
结果表明，妊娠中期暴露于B[a]P的大鼠，其后代的发育节点延迟，后代的神经感觉敏感性降低。这些后代在成年后也有认知障碍。随后的形态学和蛋白质实验表明，暴露的后代海马CA1区神经元复杂性降低，海马组织中β-连环蛋白表达减少，GSK-3β表达增加。然而，所有这些指标都可以被LiCl逆转。
这些结果表明，妊娠中期暴露于B[a]P可能通过下调Wnt/β-连环蛋白信号通路导致后代神经损伤。
