Maternal influenza A viral infections in humans are associated with low birth weight, increased risk of pre-term birth, stillbirth and congenital defects. To examine the effect of maternal influenza virus infection on placental and fetal growth, pregnant C57BL/6 mice were inoculated intranasally with influenza A virus A/CA/07/2009 pandemic H1N1 or phosphate-buffered saline (PBS) at E3.5, E7.5 or E12.5, and the placentae and fetuses collected and weighed at E18.5. Fetal thymuses were pooled from each litter. Placentae were examined histologically, stained by immunohistochemistry (IHC) for CD34 (hematopoietic progenitor cell antigen) and vascular channels quantified. RNA from E7.5 and E12.5 placentae and E7.5 fetal thymuses was subjected to RNA sequencing and pathway analysis. Placental weights were decreased in litters inoculated with influenza at E3.5 and E7.5. Placentae from E7.5 and E12.5 inoculated litters exhibited decreased labyrinth development and the transmembrane protein 150A gene was upregulated in E7.5 placentae. Fetal weights were decreased in litters inoculated at E7.5 and E12.5 compared to controls. RNA sequencing of E7.5 thymuses indicated that 957 genes were downregulated 2-fold including Mal, which is associated with Toll-like receptor signaling and T cell differentiation. There were 28 upregulated genes. It is concluded that maternal influenza A virus infection impairs fetal thymic gene expression as well as restricting placental and fetal growth.

中文翻译：

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产妇甲型流感病毒感染会限制胎儿和胎盘的生长，并不利地影响胎儿胸腺转录组。

孕妇的甲型流感病毒感染与低出生体重，早产，死产和先天性缺陷的风险增加有关。为了检查母源流感病毒感染对胎盘和胎儿生长的影响，在怀孕的C57BL / 6小鼠鼻腔内接种甲型流感病毒A / CA / 07/2009大流行H1N1或磷酸盐缓冲液（PBS），剂量分别为E3.5，E7 0.5或E12.5，收集胎盘和胎儿并称重E18.5。从每个垫料中收集胎儿胸腺。组织学检查胎盘，用免疫组织化学（IHC）染色CD34（造血祖细胞抗原）并定量血管。对来自E7.5和E12.5胎盘以及E7.5胎儿胸腺的RNA进行RNA测序和途径分析。在E3.5和E7.5接种流感的垫料中的胎盘重量降低。在E7.5胎盘中，接种E7.5和E12.5的幼仔的胎盘显示迷宫的发展减少，跨膜蛋白150A基因上调。与对照组相比，接种E7.5和E12.5的幼仔的胎儿体重降低。E7.5胸腺的RNA测序表明957个基因被下调了2倍，包括Mal，与Toll样受体信号转导和T细胞分化有关。有28个上调基因。结论是，母亲的甲型流感病毒感染会损害胎儿的胸腺基因表达，并限制胎盘和胎儿的生长。