Prenatal NO2 exposure and neurodevelopmental disorders in offspring mice: Transcriptomics reveals sex-dependent changes in cerebral gene expression.

摘要: Abstract Background Early-life exposure to nitrogen dioxide (NO2) is associated with an increased risk of developing a neurodevelopmental disorder during childhood or later in life. Objectives We investigated whether prenatal NO2 inhalation causes abnormalities and cognitive deficits weanling offspring without subsequent postnatal how this contributes consequences. Methods Pregnant C57BL/6 mice were exposed air (2.5 ppm, 5 h/day) throughout gestation, the sacrificed on days (PNDs) 1, 7, 14 21. determined mRNA profiles different developmental windows, detected long noncoding RNA (lncRNA) function offspring, analyzed effects hub lncRNAs differentially expressed genes (DEGs). Results Prenatal significantly impaired male, but not female, offspring. The male-specific response was coupled abnormal neuropathologies transcriptional cortex windows. Consistently, Gene Ontology (GO) analysis DEGs revealed persistent disruptions neurodevelopment-associated biological processes cellular components male Apolipoprotein E (ApoE) one key factors contributing exposure-induced neurological dysfunction. In addition, distinct sex-dependent lncRNA expression identified metastasis-associated lung adenocarcinoma transcript 1 (Malat1) acted as coexpressed most coding lncRNA-mRNA pairs Importantly, Malat1 elevated, modulated ApoE through NF-κB activation process. Conclusions related neurocognitive transcriptomic profile changes cortices prenatally Male-specific dysfunction constant alteration neurodevelopment their modulation by lncRNAs.