Walker Caroline G, Meier Susanne, Hussein Hassan, McDougall Scott, Burke Chris R, Roche John R, Mitchell Murray D
DairyNZ Limited, Auckland, New Zealand;
DairyNZ Limited, Hamilton, New Zealand;
Physiol Genomics. 2015 Apr;47(4):89-101. doi: 10.1152/physiolgenomics.00098.2014. Epub 2015 Jan 20.
Postpartum uterine inflammation (endometritis) in the dairy cow is associated with lower fertility at both the time of infection and after the inflammation has resolved. We hypothesized that aberrant DNA methylation may be involved in the subfertility associated with uterine inflammation. The objective of this study was to characterize genome-wide DNA methylation and gene expression in the endometrium of dairy cows with subclinical endometritis (SCE). Endometrial tissues were obtained at 29 days postpartum (n = 12), and microarrays were used to characterize transcription and DNA methylation. Analyses revealed 1,856 probes differentially expressed in animals with SCE (n = 6) compared with controls (CON, n = 6, P < 0.05, Storey Multiple testing correction) and 2,976 probes with significant correlation between gene expression and bacteriology score. No significant associations among DNA methylation and gene expression were detected. Analysis of transcription data using the Database for Annotation, Visualization, and Integrated Discovery and Gene Set Enrichment Analysis identified several pathways and processes enriched in SCE cows, with the majority related to the immune response. Furthermore, the top ontology terms enriched in genes that had expression data correlated to bacteriology score were: Defense response, inflammatory response, and innate immune response. Gene expression profiles in cows with subclinical endometritis in this study indicate that the immune response is activated, potentially resulting in a local proinflammatory environment in the uterus. If this period of inflammation is prolonged it could result in tissue damage or failure to complete involution of the uterus, which may create a suboptimal environment for future pregnancy.
奶牛产后子宫炎症（子宫内膜炎）在感染时以及炎症消退后均与繁殖力降低有关。我们推测异常的DNA甲基化可能与子宫炎症相关的生育力低下有关。本研究的目的是表征患有亚临床子宫内膜炎（SCE）的奶牛子宫内膜中的全基因组DNA甲基化和基因表达。在产后29天获取子宫内膜组织（n = 12），并使用微阵列来表征转录和DNA甲基化。分析显示，与对照组（CON，n = 6，P < 0.05，Storey多重检验校正）相比，SCE动物（n = 6）中有1856个探针差异表达，并且有2976个探针在基因表达与细菌学评分之间具有显著相关性。未检测到DNA甲基化与基因表达之间的显著关联。使用注释、可视化和综合发现数据库以及基因集富集分析对转录数据进行分析，确定了SCE奶牛中富集的几种途径和过程，其中大多数与免疫反应相关。此外，在与细菌学评分相关的表达数据的基因中富集的顶级本体术语是：防御反应、炎症反应和先天免疫反应。本研究中亚临床子宫内膜炎奶牛的基因表达谱表明免疫反应被激活，可能导致子宫局部促炎环境。如果这种炎症期延长，可能会导致组织损伤或子宫复旧不全，这可能会为未来的妊娠创造一个不理想的环境。
