Vitamin D deficiency (VDD) during pregnancy is common and related to several maternal and fetal morbidities. Vitamin D (VD) plays a role in normal lung development and VDD causes abnormal airway, alveolar, and vascular growth in newborn rats. Here we use an unbiased transcriptomic approach to identify pathways altered in the lungs of offspring from VDD dams. The lungs of newborn offspring from VD replete and VDD dams were removed and RNA from these samples were analyzed using Affymetrix microarrays. Data were RMA normalized, differential gene expression was determined using Significance Analysis of Microarrays (5 % FDR) and pathway enrichment analysis was assessed. There were 2233 differentially expressed transcripts between the VDD and control lungs (1889 up, 344 down). Consistent with the suppression of lung growth in the VDD group, there were significant suppression of signal transduction pathways related to vascular biology and anabolic signaling pathways, e.g. the insulin-like growth factor-1 receptor (IGF-1R), fibroblast growth factor (FGF), cell cycle control. A major, enriched functional category was upregulation of pathways related to the innate immune system, including pathways for granulocyte and macrophage development, chemotaxis, and activation of cytokine signaling through Jak/Stat (e.g. resulting in higher IL1 α and β). We conclude that VDD during fetal development alters multiple pathways beyond the predicted angiogeneic alterations. These changes either contribute to, or reflect, the abnormal airway, alveolar, and vascular growth seen in the neonatal lung resulting from maternal VDD. The pattern also suggests abnormal lung development caused by maternal VDD creates a proinflammatory milieu that could contribute to the suppression of lung growth and development.

中文翻译：

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母体维生素 D 缺乏会导致新生大鼠肺的转录组变化。

怀孕期间维生素 D 缺乏症 (VDD) 很常见，并且与多种母婴发病率有关。维生素 D (VD) 在正常肺发育中起作用，而 VDD 会导致新生大鼠气道、肺泡和血管生长异常。在这里，我们使用无偏见的转录组学方法来识别 VDD 水坝后代肺中改变的途径。来自 VD 充满和 VDD 坝的新生后代的肺被移除，并使用 Affymetrix 微阵列分析来自这些样品的 RNA。数据进行 RMA 标准化，使用微阵列显着性分析 (5% FDR) 确定差异基因表达，并评估通路富集分析。在 VDD 和对照肺之间有 2233 个差异表达的转录本（1889 个，344 个）。与 VDD 组肺生长的抑制一致，与血管生物学和合成代谢信号通路相关的信号转导通路受到显着抑制，例如胰岛素样生长因子-1 受体 (IGF-1R)、成纤维细胞生长因子 (FGF)、细胞周期控制。一个主要的、丰富的功能类别是与先天免疫系统相关的通路的上调，包括粒细胞和巨噬细胞发育、趋化性和通过 Jak/Stat 激活细胞因子信号传导的通路（例如导致更高的 IL1 α 和 β）。我们得出结论，胎儿发育过程中的 VDD 改变了超出预测的血管生成改变的多种途径。这些变化导致或反映了因母体 VDD 引起的新生儿肺中出现的异常气道、肺泡和血管生长。