Integrated systems approach for preventing uterine disease in dairy cattle

分娩后子宫的多病原体感染是地方性的，导致40%的奶牛出现临床子宫疾病，另外每年有20-40%的奶牛出现亚临床疾病。随着产奶量的增加，需要治疗的动物数量也在增加。子宫疾病导致不孕、受孕延迟、卵巢周期中断、因未能怀孕而非自愿淘汰和死亡，每年给欧盟乳制品行业造成14亿欧元的损失。对动物来说，代价是几个星期的痛苦和折磨。环境的代价是更多的温室气体排放，土地和水的退化，因为农场必须饲养更多的牛来取代不育的动物。与其他主要疾病相比，对子宫感染的研究一直被忽视；没有疫苗或预防策略，治疗依赖于抗生素和激素。然而，在过去的10年里，关于先天免疫和粘膜免疫的知识有了爆炸式的增长，这为预防疾病提供了新的见解。此外，我们最近的工作已经确定了几种预防或限制这种地方病的潜在战略，迫切需要加以研究。现在是战略时刻，合作伙伴之间的协调行动很可能对子宫疾病产生影响。该项目旨在将新策略转化为限制子宫疾病影响的潜在产品。我们将追求三个目标：1。完善我们对牛产后子宫疾病的基础知识和工具。这包括完善我们的体外和体内疾病模型并对其进行基准测试；探索感染子宫的微生物的细节，包括我们新发现的子宫内膜致病性大肠杆菌（EnPEC）；开发分子工具来评估和诊断疾病。2. 使用我们的体外和体内模型测试预防或限制子宫疾病的候选策略。3. 将预防或限制子宫疾病的最佳候选策略转化为临床前实地试验。该项目解决了基础科学与产生动物健康想法或产品之间的第一个转化差距。我们很幸运地得到了我们的行业合作伙伴的支持，他们也有专业知识，可以将项目的成果推向市场，使所有利益相关者受益。

Multi-pathogen infections of the uterus after parturition are endemic causing clinical uterine disease in 40% of dairy cattle and a further 20-40% develop subclinical disease each year. The number of animals requiring treatment is rising as milk production increases. Uterine disease causes infertility, delayed conception, disruption of ovarian cycles, involuntary culling for failure to conceive, and mortality, costing the EU dairy industry EURO1.4 billion/year. The cost to the animal is pain and suffering for several weeks. The cost to the environment is more greenhouse gas emissions, land and water degradation because more cattle have to be kept on farms to replace infertile animals. Research into uterine infection has been neglected compared with other major diseases; there are no vaccines or prevention strategies, and treatment relies on antibiotics and hormones. However, there has been an explosion of knowledge about innate and mucosal immunity in the last 10 years, which provides insights that can be exploited to prevent disease. Furthermore, our recent work has identified several potential strategies to prevent or limit this endemic disease that urgently need examining. Now is the strategic moment where concerted action between the partners is likely to have an impact on uterine disease. This project aims to translate novel strategies into potential products that limit the impact of uterine disease. We will pursue 3 objectives: 1. Refine our underpinning knowledge and tools for postpartum uterine disease in cattle. This includes refining and benchmarking our in vitro and in vivo models of disease; exploring the details of the microbes that infect the uterus, including our newly discovered endometrial pathogenic E. coli (EnPEC); and developing molecular tools to evaluate and diagnose disease. 2. Test candidate strategies to prevent or limit uterine disease using our in vitro and in vivo models. 3. Translate the best candidate strategies that prevent or limit uterine disease to pre-clinical field trials. The project addresses the first translational gap between basic science and the generation of ideas or products for animal health. We are fortunate to have support from our industrial partners, who also have the expertise to then take the results of the project to market for the benefit of all stakeholders.