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Published on: May 4, 2020
Prenatal NO2 Exposure and Bronchopulmonary Dysplasia in Offspring: ceRNA Network-Mediated Cell Cycle Dysregulation in
Liyao Qin1, Wei Yan2, Huifeng Yue1
1Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China.
Abstract:
Epidemiological studies have established a correlation between prenatal nitrogen dioxide (NO2) exposure and the incidence of respiratory diseases in offspring. However, the sex-specific outcomes of respiratory system development, critical risk windows, and underlying epigenetic mechanisms remain unclear. In this study, we established a prenatal NO2 exposure model and found that prenatal NO2 exposure induced pulmonary dysfunction and structural abnormalities in neonatal offspring (particularly airflow limitation, airway obstruction, and alveolar development) and impaired airway secretory functions and angiogenesis. These alterations resulted in bronchopulmonary dysplasia (BPD)-like symptoms on postnatal day 14 in a sex-independent manner. Transcriptomic analysis of lung tissues from prenatal NO2-exposed and BPD model mice revealed that differentially expressed genes were significantly enriched in cell-cycle-related biological processes. We further confirmed that prenatal NO2 exposure disrupted the cell cycle in alveolar type II (AT2) cells. Mechanistically, prenatal NO2 exposure elevated hypoxia-inducible factor 1α (HIF-1α) expression in the lungs of neonatal offspring, which disrupted the transcription of long non-coding RNA (lncRNA) NONMMUT016369.2 and changed the expression of cell cycle-related genes (E2f8 and Cep55) through a competing endogenous RNA (ceRNA) mechanism, thereby contributing to structural and functional lung impairments and ultimately promoting the development of BPD in offspring. This study provides experimental evidence for the respiratory health risk in offspring posed by prenatal NO2 exposure and reveals a potential intervention target for prevention.
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