4.6 Article

Airborne fine particulate matter induces cognitive and emotional disorders in offspring mice exposed during pregnancy

Journal

SCIENCE BULLETIN
Volume 66, Issue 6, Pages 578-591

Publisher

ELSEVIER
DOI: 10.1016/j.scib.2020.08.036

Keywords

Airborne fine particulate matter; Gestational exposure; Lipid metabolism; Mass spectrometry imaging; Cognitive and emotional disorders

Funding

  1. National Natural Science Foundation of China [91843301]
  2. National Key Research Program of China [2017YFC1600505, 2017YFE0191000]
  3. Sanming Project of Medicine in Shenzhen of China [SZSM201811070]
  4. General Research Fund from Hong Kong Research Grants Council [12303320]

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The study revealed that gestational exposure to PM2.5 can result in cognitive and emotional disorders in offspring, even if the offspring were not directly exposed to PM2.5. Neurodegeneration in the hippocampus, impairment of placental cytoarchitecture, and reprogramming of lipidome induced by PM2.5 exposure may affect maternal-fetal cross-talk and lead to behavioral disorders in offspring.
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. (C) 2020 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.

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