Lung growth is a critical window, when exposure to various pollutants can disturb the finely-tuned lung development and enhance risk of long-term structural and functional sequelae of lung. In this study, pregnant C57/6 mice were treated with NO₂, and lungs of fetus/offspring were collected at different developmental windows and dynamic lung development was determined. The results showed that maternal NO₂ exposure suppressed fetal weight, implying that fetal development can be disturbed. The time-series RNA-seq analysis of lungs showed that maternal NO₂ exposure induced significant time-dependent changes in the expression profiles of genes associated with lung vein myocardium development in fetus/offspring. Most of these genes in NO₂ exposure group were suppressed at middle gestation and at birth. Our results also indicated that the gene expressions of Nkx2.5 in NO₂ exposure were suppressed to 0.27- and 0.44-fold of the corresponding Air group at E13.5 and PND1, and restored at later time points. This indicated that the transcription factor Nkx2.5 played an important role in abnormal lung development in fetus/offspring caused by maternal NO₂ exposure. Importantly, gene expressions of lung vein myocardium development were related to transcription factors (TFs) and lung functions, and TFs showed similar trends with lung function. These results provide a comprehensive view of the adverse effects of maternal NO₂ exposure on fetal lung development by uncovering molecular targets and related signaling pathways at the transcriptional level.

肺部生长是一个关键的窗口期，接触各种污染物会扰乱肺部的精细发育，并增加肺部长期结构和功能后遗症的风险。_{在本研究中，用NO 2}处理怀孕的C57/6小鼠，并在不同发育窗口收集胎儿/后代的肺并测定动态肺发育。结果表明，母体NO ₂暴露会抑制胎儿体重，这意味着胎儿发育可能会受到干扰。肺部的时间序列RNA-seq分析表明，母体NO ₂暴露会导致胎儿/后代肺静脉心肌发育相关基因的表达谱发生显着的时间依赖性变化。_{NO 2}暴露组中的大多数这些基因在妊娠中期和出生时受到抑制。我们的结果还表明， NO ₂暴露中Nkx2.5的基因表达在 E13.5 和 PND1 时被抑制至相应 Air 组的 0.27 和 0.44 倍，并在以后的时间点恢复。这表明转录因子Nkx2.5在母体NO ₂暴露引起的胎儿/子代肺发育异常中发挥了重要作用。重要的是，肺静脉心肌发育的基因表达与转录因子（TF）和肺功能相关，并且TF与肺功能表现出相似的趋势。这些结果通过揭示转录水平上的分子靶标和相关信号通路，全面了解母体 NO _{2暴露对胎儿肺部发育的不利影响。}