Modulation of the immune system is known to be important for successful pregnancy but how immune function might differ between the lymph nodes draining the reproductive tract and peripheral lymph nodes is not well understood. Additionally, if immune system changes in response to the presence of an embryo during early pregnancy, and if this response differs in local versus peripheral immune tissue, has not been well characterized. To address these questions, we examined expression of genes important for immune function using NanoString technology in the ampulla and isthmus of the oviduct, endometrium, lymph nodes draining the reproductive tract (lumbo-aortic and medial iliac) as well as a peripheral lymph node (axillary), the spleen, and circulating immune cells from ewes on day 5 of the estrous cycle or pregnancy. Concentrations of estradiol and progesterone in plasma were also determined. Principal component analysis revealed separation of the local from the peripheral lymph nodes (MANOVA P = 3.245e-08, R2 = 0.3) as well as separation of tissues from pregnant and nonpregnant animals [lymph nodes (MANOVA P = 2.337e-09, R2 = 0.5), reproductive tissues (MANOVA P = 2.417e-14, R2 = 0.47)]. Nine genes were differentially (FDR < 0.10) expressed between lymph node types, with clear difference in expression of these genes between the lumbo-aortic and axillary lymph nodes. Expression of these genes in the medial iliac lymph node was not consistently different to either the axillary or the lumbo-aortic lymph node. Expression of IL10RB was increased (FDR < 0.05) by 24% in the reproductive tissue of the pregnant animals compared to nonpregnant animals. Analysis of gene categories revealed that expression of genes of the T-cell receptor pathway in reproductive tract tissues was associated (P < 0.05) with pregnancy status. In conclusion, assessment of gene expression of reproductive and immune tissue provides evidence for a specialization of the local immune system around the reproductive tract potentially important for successful establishment of pregnancy. Additionally, differences in gene expression patterns in reproductive tissue from pregnant and nonpregnant animals could be discerned as early as day 5 of pregnancy. This was found to be associated with expression of genes important for T-cell function and thus highlights the important role of these cells in early pregnancy.

中文翻译：

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妊娠和未妊娠母羊局部和外周免疫系统的表征

众所周知，调节免疫系统对成功怀孕很重要，但引流生殖道的淋巴结和外周淋巴结之间的免疫功能可能有何不同尚不清楚。此外，如果免疫系统在妊娠早期对胚胎的存在做出反应，并且这种反应在局部免疫组织与外周免疫组织中不同，则尚未得到很好的表征。为了解决这些问题，我们使用 NanoString 技术检查了输卵管壶腹和峡部、子宫内膜、引流生殖道淋巴结（腰主动脉和髂内动脉）以及外周淋巴结中免疫功能重要基因的表达。在发情周期或妊娠的第 5 天，来自母羊的腋窝）、脾脏和循环免疫细胞。还测定了血浆中雌二醇和孕酮的浓度。主成分分析显示局部淋巴结与外周淋巴结的分离 (MANOVA P = 3.245e-08, R2 = 0.3) 以及妊娠和非妊娠动物的组织分离 [淋巴结 (MANOVA P = 2.337e-09, R2) = 0.5)，生殖组织 (MANOVA P = 2.417e-14, R2 = 0.47)]。九个基因在淋巴结类型之间差异表达（FDR < 0.10），这些基因在腰主动脉和腋窝淋巴结之间的表达存在明显差异。这些基因在内侧髂淋巴结中的表达与腋窝或腰主动脉淋巴结并不一致。与未怀孕的动物相比，怀孕动物的生殖组织中 IL10RB 的表达增加了 24% (FDR < 0.05)。基因类别分析显示，生殖道组织中 T 细胞受体途径基因的表达与妊娠状态相关（P < 0.05）。总之，生殖和免疫组织基因表达的评估为生殖道周围局部免疫系统的特化提供了证据，这对于成功怀孕可能很重要。此外，早在怀孕第 5 天就可以发现怀孕和未怀孕动物生殖组织中基因表达模式的差异。这被发现与对 T 细胞功能重要的基因的表达有关，因此突出了这些细胞在妊娠早期的重要作用。