University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, 4029, Australia.
Institute of Health and Biomedical Innovation - Centre for Children's Health Research, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, 4101, Australia.
Sci Rep. 2019 Sep 25;9(1):13879. doi: 10.1038/s41598-019-50244-7.
Disease susceptibility of dairy cows is greatest during the transition from pregnancy to lactation. Circulating exosomes may provide biomarkers to detect at-risk cows to enhance health and productivity. From 490 cows, animals at high- (n = 20) or low-risk (n = 20) of transition-related diseases were identified using plasma non-esterified fatty acid and β-hydroxybutyrate concentrations and liver triacylglyceride concentrations during the two weeks post-calving. We isolated circulating exosomes from plasma of dairy cows at low-risk (LR-EXO) and high-risk (HR-EXO), and analyzed their proteome profiles to determine markers for metabolic dysfunction. We evaluated the effects of these exosomes on eicosanoid pathway expression by bovine endometrial stromal (bCSC) and epithelial (bEEL) cells. HR-EXO had significantly lower yield of circulating exosomes compared with LR-EXO, and unique proteins were identified in HR-EXO and LR-EXO. Exposure to LR-EXO or HR-EXO differentially regulated eicosanoid gene expression and production in bCSC and bEEL cells. In bCSC, LR-EXO exposure increased PGE and PGD production, whereas HR-EXO exposure increased PTGS2 gene expression. In bEEL, HR-EXO exposure caused a decrease in PGE PGF, PGD, PGFM and TXB production. The unique presence of serpin A3-7, coiled-coil domain containing 88A and inhibin/activin β A chain in HR-EXO, indicates potential biomarkers for cows at-risk for metabolic diseases. Our results are in line with the health status of the cow indicating a potential diagnostic role for exosomes in enhancing cows' health and fertility.
奶牛在妊娠向泌乳过渡期间易患疾病。循环外泌体可能为检测高危奶牛提供生物标志物，以增强其健康和生产力。从 490 头奶牛中，根据产后两周内的血浆非酯化脂肪酸和β-羟丁酸浓度以及肝三酰甘油浓度，鉴定出处于与过渡相关疾病高（n=20）或低（n=20）风险的动物。我们从处于低风险（LR-EXO）和高风险（HR-EXO）的奶牛的血浆中分离出循环外泌体，并分析其蛋白质组谱，以确定代谢功能障碍的标志物。我们评估了这些外泌体对牛子宫内膜基质（bCSC）和上皮（bEEL）细胞中花生四烯酸途径表达的影响。与 LR-EXO 相比，HR-EXO 中循环外泌体的产量明显较低，并且在 HR-EXO 和 LR-EXO 中鉴定出独特的蛋白质。LR-EXO 或 HR-EXO 的暴露以不同的方式调节 bCSC 和 bEEL 细胞中的花生四烯酸基因表达和产生。在 bCSC 中，LR-EXO 暴露增加了 PGE 和 PGD 的产生，而 HR-EXO 暴露增加了 PTGS2 基因表达。在 bEEL 中，HR-EXO 暴露导致 PGE、PGF、PGD、PGFM 和 TXB 产生减少。HR-EXO 中独特存在的丝氨酸蛋白酶抑制剂 A3-7、卷曲螺旋结构域包含 88A 和抑制素/激活素βA 链，表明这是代谢疾病高危奶牛的潜在生物标志物。我们的结果与奶牛的健康状况一致，表明外泌体在增强奶牛健康和生育能力方面具有潜在的诊断作用。
