Department of Animal Sciences, University of Florida, Gainesville, FL, United States of America.
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United States of America.
PLoS One. 2022 Mar 31;17(3):e0265062. doi: 10.1371/journal.pone.0265062. eCollection 2022.
Pregnancy induces changes in the transcriptome of the bovine endometrium from 15 days after insemination. However, pregnancy is less likely to occur if cows had a postpartum bacterial infection of the uterus, even after the resolution of disease. We hypothesized that uterine bacterial infection alters the endometrial transcriptomic signature of pregnancy after the resolution of disease. To examine the endometrial transcriptomic signature of pregnancy, cows were inseminated 130 days after intrauterine infusion of pathogenic Escherichia coli and Trueperella pyogenes, subsequently endometrium was collected 16 days after insemination for RNA sequencing. We found 171 pregnancy regulated genes in cows 146 days after bacterial infection. When comparing our findings with previous studies that described the endometrial transcriptomic signature of pregnancy in healthy cows, 24 genes were consistently differentially expressed in pregnancy, including MX1, MX2 and STAT1. However, 12 pregnancy regulated genes were found only in the endometrium of healthy cows, including ISG15 and TRANK1. Furthermore, 28 pregnancy regulated genes were found only in the endometrium of cows following bacterial infection and these were associated with altered iNOS, TLR, and IL-7 signaling pathways. Although 94 predicted upstream regulators were conserved amongst the studies, 14 were found only in the endometrium of pregnant healthy cows, and 5 were found only in cows following bacterial infection, including AIRE, NFKBIA, and DUSP1. In conclusion, there were both consistent and discordant features of the endometrial transcriptomic signature of pregnancy 146 days after intrauterine bacterial infusion. These findings imply that there is an essential transcriptomic signature of pregnancy, but that infection induces long-term changes in the endometrium that affect the transcriptomic response to pregnancy.
妊娠会导致牛子宫内膜在受精后 15 天的转录组发生变化。然而，如果牛在产后发生子宫细菌感染，即使疾病得到解决，妊娠的可能性也会降低。我们假设子宫细菌感染会改变疾病解决后妊娠的子宫内膜转录组特征。为了检查妊娠的子宫内膜转录组特征，我们在宫内输注致病性大肠杆菌和 Trueperella pyogenes 后 130 天给奶牛授精，随后在授精后 16 天收集子宫内膜进行 RNA 测序。我们发现，在细菌感染 146 天后的奶牛中，有 171 个妊娠调节基因。当将我们的发现与先前描述健康奶牛妊娠子宫内膜转录组特征的研究进行比较时，有 24 个基因在妊娠中一致差异表达，包括 MX1、MX2 和 STAT1。然而，只有在健康奶牛的子宫内膜中发现了 12 个妊娠调节基因，包括 ISG15 和 TRANK1。此外，只有在细菌感染后的奶牛子宫内膜中发现了 28 个妊娠调节基因，这些基因与 iNOS、TLR 和 IL-7 信号通路的改变有关。尽管在这些研究中有 94 个预测的上游调节剂是保守的，但只有 14 个在妊娠健康奶牛的子宫内膜中发现，只有 5 个在细菌感染后的奶牛中发现，包括 AIRE、NFKBIA 和 DUSP1。总之，在宫内细菌输注后 146 天，子宫内膜妊娠转录组特征既有一致的特征，也有不一致的特征。这些发现表明，妊娠存在基本的转录组特征，但感染会导致子宫内膜长期变化，从而影响对妊娠的转录组反应。
