Prenatal exposure to air pollutants is associated with increased risk for neurodevelopmental and neurodegenerative disorders. However, few studies have identified transcriptional changes related to air pollutant exposure. RNA sequencing was used to examine transcriptomic changes in blood and cerebral cortex of three male and three female mouse neonates prenatally exposed to traffic-related nano-sized particulate matter (nPM) compared to three male and three female mouse neonates prenatally exposed to control filter air. We identified 19 nPM-associated differentially expressed genes (nPM-DEGs) in blood and 124 nPM-DEGs in cerebral cortex. The cerebral cortex transcriptional responses to nPM suggested neuroinflammation involvement, including CREB1, BDNF, and IFNγ genes. Both blood and brain tissues showed nPM transcriptional changes related to DNA damage, oxidative stress, and immune responses. Three blood nPM-DEGs showed a canonical correlation of 0.98 with 14 nPM-DEGS in the cerebral cortex, suggesting a convergence of gene expression changes in blood and cerebral cortex. Exploratory sex-stratified analyses suggested a higher number of nPM-DEGs in female cerebral cortex than male cerebral cortex. The sex-stratified analyses identified 2 nPM-DEGs (Rgl2 and Gm37534) shared between blood and cerebral cortex in a sex-dependent manner. Our findings suggest that prenatal nPM exposure induces transcriptional changes in the cerebral cortex, some of which are also observed in blood. Further research is needed to replicate nPM-induced transcriptional changes with additional biologically relevant time points for brain development.

中文翻译：

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出生前暴露于空气污染颗粒物的小鼠新生儿的大脑皮层和血液转录组变化

产前暴露于空气污染物与神经发育和神经退行性疾病的风险增加有关。然而，很少有研究确定与空气污染物暴露相关的转录变化。与产前暴露于控制过滤空气的三只雄性和三只雌性小鼠新生儿相比，RNA 测序用于检查出生前暴露于交通相关纳米颗粒物质 (nPM) 的三只雄性和三只雌性小鼠新生儿的血液和大脑皮层的转录组变化. 我们在血液中鉴定了 19 个与 nPM 相关的差异表达基因 (nPM-DEG)，在大脑皮层中鉴定出 124 个 nPM-DEG。大脑皮层对 nPM 的转录反应表明涉及神经炎症，包括 CREB1、BDNF 和 IFNγ 基因。血液和脑组织均显示出与 DNA 损伤、氧化应激和免疫反应相关的 nPM 转录变化。三个血液 nPM-DEG 与大脑皮层中的 14 个 nPM-DEGS 显示出 0.98 的典型相关性，表明血液和大脑皮层中基因表达变化的收敛。探索性性别分层分析表明，女性大脑皮层中的 nPM-DEG 数量高于男性大脑皮层。性别分层分析确定了血液和大脑皮层之间以性别依赖性方式共享的 2 个 nPM-DEG（Rgl2 和 Gm37534）。我们的研究结果表明，产前 nPM 暴露会诱导大脑皮层的转录变化，其中一些也在血液中观察到。