An intravenous large dose of protein led to an increased blood urea nitrogen (BUN), resulting in a lesser uterine pH and altered uterine gene expression in mares. The objective of the present study was to evaluate effects of a more physiological methodology to increase BUN on the endometrium of mares. Mares were fed hay and a treatment or control diet (n = 11 mares/treatment) in a crossover design starting at time of ovulation detection (D0) and continuing until D7. Mares of the treated group were fed urea (0.4 g/kg BW) with sweet feed and molasses, and those of the control group were fed sweet feed and molasses. Blood samples were collected daily, 1 hour after feeding, for BUN determination. Uterine and vaginal pH were determined after the last feeding on D7, and endometrial biopsies were performed. The RNA sequencing of the endometrium of a subset of mares (n = 6/treatment) was conducted. Differentially expressed genes (DEGs) between treatments were calculated (FDR-adjusted P-value<0.1). Urea-treated mares had greater BUN (P < 0.05), with no differences in uterine and vaginal pH compared to control mares. A total of 60 DEGs were characterized, those with largest fold change were SIK1, ATF3, SPINK7, NR4A1 and EGR3. Processes related to necrosis and cellular movement were predicted with the DEGs. Dietary administration of urea resulted in transcriptomic changes in the endometrium of mares related to necrosis, tissue remodeling and concentration of lipids. The observed changes in gene expression after an increased BUN might result in a disruption to the endometrium.

中文翻译：

---

口服尿素对母体子宫内膜转录组的影响。

静脉内大剂量蛋白质导致血液尿素氮（BUN）升高，导致子宫pH值降低和母马子宫基因表达改变。本研究的目的是评估一种更生理的方法来增加BUN对母马子宫内膜的影响。母猪饲喂干草和处理或对照饮食（n = 11母马/处理），采用交叉设计，从排卵检测（D0）开始，一直持续到D7。治疗组母马饲喂含甜饲料和糖蜜的尿素（0.4 g / kg BW），对照组母猪饲喂甜饲料和糖蜜。每天在喂食后1小时收集血样用于BUN测定。在最后一次喂食D7后确定子宫和阴道的pH，并进行子宫内膜活检。进行了一部分母马子宫内膜的RNA测序（n = 6 /次）。计算治疗之间的差异表达基因（DEG）（FDR调整后的P值<0.1）。经尿素处理的母马与对照母马相比，​​BUN更大（P <0.05），子宫和阴道pH值无差异。共鉴定了60个DEG，折叠变化最大的是SIK1，ATF3，SPINK7，NR4A1和EGR3。DEGs预测了与坏死和细胞运动有关的过程。饮食中尿素的给药导致母马子宫内膜转录组的变化，与坏死，组织重塑和脂质浓度有关。BUN升高后观察到的基因表达变化可能导致子宫内膜破裂。计算治疗之间的差异表达基因（DEG）（FDR调整后的P值<0.1）。经尿素处理的母马与对照母马相比，​​BUN更大（P <0.05），子宫和阴道pH值无差异。共鉴定了60个DEG，折叠变化最大的是SIK1，ATF3，SPINK7，NR4A1和EGR3。DEGs预测了与坏死和细胞运动有关的过程。饮食中尿素的给药导致母马子宫内膜转录组的变化，与坏死，组织重塑和脂质浓度有关。BUN增加后观察到的基因表达变化可能导致子宫内膜破裂。计算治疗之间的差异表达基因（DEG）（FDR调整后的P值<0.1）。经尿素处理的母马与对照母马相比，​​BUN更大（P <0.05），子宫和阴道pH值无差异。总共鉴定了60个DEG，折叠变化最大的是SIK1，ATF3，SPINK7，NR4A1和EGR3。DEGs预测了与坏死和细胞运动有关的过程。饮食中尿素的给药导致母马子宫内膜转录组的变化，与坏死，组织重塑和脂质浓度有关。BUN增加后观察到的基因表达变化可能导致子宫内膜破裂。与对照组母马相比，​​子宫和阴道pH值没有差异。共鉴定了60个DEG，折叠变化最大的是SIK1，ATF3，SPINK7，NR4A1和EGR3。DEGs预测了与坏死和细胞运动有关的过程。尿素的饮食管理导致母马子宫内膜转录组的变化，与坏死，组织重塑和脂质浓度有关。BUN增加后观察到的基因表达变化可能导致子宫内膜破裂。与对照组母马相比，​​子宫和阴道pH值没有差异。总共鉴定了60个DEG，折叠变化最大的是SIK1，ATF3，SPINK7，NR4A1和EGR3。DEGs预测了与坏死和细胞运动有关的过程。饮食中尿素的给药导致母马子宫内膜转录组的变化，与坏死，组织重塑和脂质浓度有关。BUN增加后观察到的基因表达变化可能导致子宫内膜破裂。饮食中尿素的给药导致母马子宫内膜转录组的变化，与坏死，组织重塑和脂质浓度有关。BUN增加后观察到的基因表达变化可能导致子宫内膜破裂。尿素的饮食管理导致母马子宫内膜转录组的变化，与坏死，组织重塑和脂质浓度有关。BUN增加后观察到的基因表达变化可能导致子宫内膜破裂。