PCB52 exposure alters the neurotransmission ligand-receptors in male offspring and contributes to sex-specific neurodevelopmental toxicity.
PCB52 exposure alters the neurotransmission ligand-receptors in male offspring and contributes to sex-specific neurodevelopmental toxicity.
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DOI：
10.1016/j.envpol.2020.114715
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发表时间：
2020-05
影响因子：
8.9
通讯作者：
Dong Zhao;Qi Wang;Wen-Tao Zhou;Li-Bin Wang;Hao Yu;Kai-kai Zhang;Lijian Chen;Xiao-Li Xie
中科院分区：
文献类型：
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作者：
Dong Zhao;Qi Wang;Wen-Tao Zhou;Li-Bin Wang;Hao Yu;Kai-kai Zhang;Lijian Chen;Xiao-Li Xie
空气中的多氯联苯 (PCB) 主要是氯化程度较低的同系物。非二恶英类 (NDL) 低氯化 PCB 的神经毒性更强，会导致人类神经发育和神经行为改变。然而，这种神经发育毒性的潜在机制仍然未知。在本研究中，从妊娠第 7 天到出生后第 21 天，对 Wistar 大鼠进行 PCB52（1 毫克/千克体重）或玉米油灌胃治疗。 PCB52 治疗后乳鼠出生时的体长和体重均显着下降，表明存在发育毒性。尽管在大脑中没有观察到明显的组织病理学变化，但使用 RNA 测序，在 PCB52 处理的雄性后代的纹状体中发现了 208 个差异表达基因 (DEG)，而在雌性后代中仅发现了 13 个 DEG，这表明存在性别特异性效应。此外，使用基因本体富集分析，从雄性后代的 208 个 DEG 中丰富了神经发育过程、神经行为改变和神经传递变化。同样，使用京都基因和基因组百科全书富集分析，神经活性配体受体相互作用和多种突触通路在雄性后代中富集，这意味着神经传递系统的功能障碍。使用蛋白质印迹方法还发现纹状体、大脑皮层和海马中这些配体受体的蛋白质表达减少。综上所述，我们的研究结果表明，妊娠期和哺乳期的 PCB52 暴露会导致具有性别偏见的男性后代神经传递配体受体的异常表达，这可能会导致神经发育毒性。
Polychlorinated biphenyls (PCBs) in the air are predominantly the less chlorinated congeners. Non-dioxin-like (NDL) low-chlorinated PCBs are more neurotoxic, and cause neurodevelopmental and neurobehavioral alterations in humans. However, the underlying mechanisms for this neurodevelopmental toxicity remain unknown. In the present study, Wistar rats were treated by gavage with PCB52 (1 mg/kg body weight) or corn oil from gestational day 7 to postnatal day 21. Both the body lengths and weights of the suckling rats at birth were significantly decreased by PCB52 treatment, suggesting developmental toxicity. Although no obvious histopathological changes were observed in the brain, using RNA-sequencing, 208 differentially expressed genes (DEGs) were identified in the striatum of PCB52-treated male offspring, while just 13 DEGs were identified in female offspring, suggesting sex-specific effects. Furthermore, using Gene Ontology enrichment analysis, neurodevelopmental processes, neurobehavioral alterations, and neurotransmission changes were enriched from the 208 DEGs in male offspring. Similarly, using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, neuroactive ligand receptor interactions and multiple synapse pathways were enriched in male offspring, implying dysfunction of the neurotransmission system. Reductions in the protein expressions of these ligand receptors were also identified in the striatum, cerebral cortex, and hippocampus using western blotting methods. Taken together, our findings indicate that PCB52 exposure during gestation and lactation results in the abnormal expression of neurotransmission ligand-receptors in male offspring with a sex bias, and that this may contribute to neurodevelopmental toxicity.