Department of Animal Sciences, DH Barron Reproductive and Perinatal Biology Research Program, University of Florida, Gainesville, FL, USA.
Metabolomics Department, Beaumont Health, Royal Oak, MI, USA.
Biol Reprod. 2023 Oct 13;109(4):415-431. doi: 10.1093/biolre/ioad088.
Endometrial inflammation is associated with reduced pregnancy per artificial insemination (AI) and increased pregnancy loss in cows. It was hypothesized that induced endometritis alters histotroph composition and induces inflammatory signatures on conceptus that compromise development. In Experiment 1, lactating cows were assigned to control (CON; n = 23) or to an intrauterine infusion of Escherichia coli and Trueperella pyogenes (ENDO; n = 34) to induce endometritis. Cows received AI 26 days after treatment, and the uterine fluid and conceptuses were collected on day 16 after AI. In Experiment 2, Holstein heifers were assigned to CON (n = 14) or ENDO (n = 14). An embryo was transferred on day 7 of the estrous cycle, and uterine fluid and conceptuses were recovered on day 16. Composition of histotroph and trophoblast and embryonic disc gene expression were assessed. Bacterial-induced endometritis in lactating cows altered histotroph composition and pathways linked to phospholipid synthesis, cellular energy production, and the Warburg effect. Also, ENDO reduced conceptus length in cows and altered expression of genes involved in pathogen recognition, nutrient uptake, cell growth, choline metabolism, and conceptus signaling needed for maternal recognition of pregnancy. The impact of ENDO was lesser on conceptuses from heifers receiving embryo transfer; however, the affected genes and associated pathways involved restricted growth and increased immune response similar to the observed responses to ENDO in conceptuses from lactating cows. Bacterial-induced endometrial inflammation altered histotroph composition, reduced conceptus growth, and caused embryonic cells to activate survival rather than anabolic pathways that could compromise development.
子宫内膜炎与人工授精（AI）每周期妊娠率降低和奶牛妊娠丢失增加有关。据推测，诱导的子宫内膜炎会改变组织营养成分，并在胚胎上诱导炎症特征，从而影响胚胎发育。在实验 1 中，将泌乳奶牛分为对照组（CON；n = 23）或大肠杆菌和腐生真杆菌宫内灌注组（ENDO；n = 34）以诱导子宫内膜炎。处理后 26 天进行 AI，AI 后第 16 天收集子宫液和胚胎。在实验 2 中，将荷斯坦小母牛分为对照组（CON；n = 14）或 ENDO 组（n = 14）。发情周期第 7 天移植胚胎，AI 后第 16 天回收子宫液和胚胎。评估组织营养和滋养层及胚胎盘基因表达的组成。泌乳奶牛的细菌诱导性子宫内膜炎改变了组织营养成分和与磷脂合成、细胞能量产生和瓦博格效应相关的途径。此外，ENDO 还降低了奶牛胚胎的长度，并改变了与病原体识别、营养吸收、细胞生长、胆碱代谢和胚胎信号转导相关的基因表达，这些基因表达对于母体识别妊娠是必需的。接受胚胎移植的小母牛的 ENDO 对胚胎的影响较小；然而，受影响的基因和相关途径涉及限制生长和增加免疫反应，这与在泌乳奶牛胚胎中观察到的对 ENDO 的反应相似。细菌诱导的子宫内膜炎症改变了组织营养成分，降低了胚胎生长，并导致胚胎细胞激活存活而不是合成代谢途径，这可能会影响胚胎发育。
