Zhao Chao, Xie Peisi, Yong Ting, Huang Wei, Liu Jianjun, Wu Desheng, Ji Fenfen, Li Min, Zhang Doudou, Li Ruijin, Dong Chuan, Ma Juan, Dong Zheng, Liu Sijin, Cai Zongwei
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong 999077, China.
Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518000, China.
Sci Bull (Beijing). 2021 Mar 30;66(6):578-591. doi: 10.1016/j.scib.2020.08.036. Epub 2020 Aug 28.
Gestational exposure to PM is associated with adverse postnatal outcomes. PM can enter alveoli by using intratracheal instillation, even penetrate through lung cells into the blood circulation. Subsequently, they are transferred across the placenta and fetal blood brain barrier, causing the adverse birth outcomes of offspring. This study demonstrated that the gestational exposure resulted in cognitive and emotional disorders in female offspring although the offspring were not exposed to PM. Placental metabolic pathways modulated fetal brain development and played a pivotal role for maternal-placental-fetal interactions in the fetal programming of adult behavioral and mental disorders. Samples of fetus, offspring hippocampus and placenta from the mice exposed to PM were investigated using a comprehensive approach including mass spectrometry-based lipidomics and three-dimensional imaging. The exposure induced the neuro-degeneration in hippocampus, impairment of placental cytoarchitecture, and reprogramming of lipidome, which might affect the modulation of maternal-fetal cross-talk and result in the behavior disorders of offspring. The variation of spatial distribution of lipids was profoundly affected in dorsal pallium and hippocampal formation regions of fetal brain, offspring hippocampus, as well as labyrinth and junctional zones of placenta. The abundance alteration of lipid markers associated with neurodegenerative diseases was validated in transgenic mouse model with Alzheimer's disease and human cerebrospinal fluid from patients with Parkinson's disease. The finding could help with the selection of more suitable heterogeneous-related substructures targeting PM exposure and the exploration of PM-induced toxicological effects on neurodegenerative diseases.
孕期暴露于细颗粒物（PM）与不良产后结局相关。PM可通过气管内滴注进入肺泡，甚至穿透肺细胞进入血液循环。随后，它们会穿过胎盘和胎儿血脑屏障，导致后代出现不良出生结局。本研究表明，尽管后代未暴露于PM，但孕期暴露会导致雌性后代出现认知和情绪障碍。胎盘代谢途径调节胎儿大脑发育，在成人性行为和精神障碍的胎儿编程中，对母-胎-胎盘相互作用起着关键作用。采用基于质谱的脂质组学和三维成像等综合方法，对暴露于PM的小鼠的胎儿、后代海马体和胎盘样本进行了研究。这种暴露会诱导海马体神经退行性变、胎盘细胞结构损伤以及脂质组重编程，这可能会影响母胎间的信号交流调节，导致后代行为障碍。在胎儿大脑的背侧皮层和海马结构区域、后代海马体以及胎盘的迷路和连接区，脂质的空间分布变化受到了深远影响。在患有阿尔茨海默病的转基因小鼠模型和帕金森病患者的人类脑脊液中，与神经退行性疾病相关的脂质标志物丰度变化得到了验证。这一发现有助于选择更合适的针对PM暴露的异质性相关亚结构，并探索PM对神经退行性疾病的毒理学效应。
