TY - JOUR
T1 - Airborne fine particulate matter induces cognitive and emotional disorders in offspring mice exposed during pregnancy
AU - Zhao, Chao
AU - Xie, Peisi
AU - Yong, Ting
AU - Huang, Wei
AU - Liu, Jianjun
AU - Wu, Desheng
AU - Ji, Fenfen
AU - Li, Min
AU - Zhang, Doudou
AU - Li, Ruijin
AU - Dong, Chuan
AU - Ma, Juan
AU - Dong, Zheng
AU - Liu, Sijin
AU - Cai, Zongwei
N1 - Funding Information:
The work was supported by the National Natural Science Foundation of China (91843301), the National Key Research Program of China (2017YFC1600505 and 2017YFE0191000), Sanming Project of Medicine in Shenzhen of China (SZSM201811070), and General Research Fund from Hong Kong Research Grants Council (12303320). We thank Bruker Daltonics for their help with data processing of MSI. Chao Zhao, Peisi Xie, Ting Yong and Wei Huang performed the animal experiments. Chao Zhao, Peisi Xie and Ting Yong performed the experiments of LC-MS/MS analysis, MALDI-MSI, morphology and molecular biology experiments. Ruijin Li and Chuan Dong collected the PM2.5 samples. Jianjun Liu and Desheng Wu contributed to the design of animal model and facility use for animal exposure. Fenfen Ji, Min Li and Doudou Zhang provided the AD mice and human CSF samples. Ruijin Li, Chuan Dong, Juan Ma, Zheng Dong and Sijin Liu provided consultancy, discussion and confirmation experiments in PM2.5 sample analysis and biological analysis. Chao Zhao and Zongwei Cai co-wrote the manuscript and analyzed the data. Zongwei Cai supervised and directed the study.
Funding Information:
The work was supported by the National Natural Science Foundation of China ( 91843301 ), the National Key Research Program of China (2017YFC1600505 and 2017YFE0191000), Sanming Project of Medicine in Shenzhen of China (SZSM201811070), and General Research Fund from Hong Kong Research Grants Council (12303320). We thank Bruker Daltonics for their help with data processing of MSI.
PY - 2021/3/30
Y1 - 2021/3/30
N2 - Gestational exposure to PM2.5 is associated with adverse postnatal outcomes. PM2.5 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 PM2.5. 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 PM2.5 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 PM2.5 exposure and the exploration of PM2.5-induced toxicological effects on neurodegenerative diseases.
AB - Gestational exposure to PM2.5 is associated with adverse postnatal outcomes. PM2.5 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 PM2.5. 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 PM2.5 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 PM2.5 exposure and the exploration of PM2.5-induced toxicological effects on neurodegenerative diseases.
KW - Airborne fine particulate matter
KW - Cognitive and emotional disorders
KW - Gestational exposure
KW - Lipid metabolism
KW - Mass spectrometry imaging
UR - http://www.scopus.com/inward/record.url?scp=85090983729&partnerID=8YFLogxK
U2 - 10.1016/j.scib.2020.08.036
DO - 10.1016/j.scib.2020.08.036
M3 - Journal article
AN - SCOPUS:85090983729
SN - 2095-9273
VL - 66
SP - 578
EP - 591
JO - Science Bulletin
JF - Science Bulletin
IS - 6
ER -