RAPID: Elevated in Utero Temperature: A Suppressor of Fetal Development and Ruminant Fitness?

RAPID：子宫内温度升高：胎儿发育和反刍动物健康的抑制因素？

• 批准号: 1247362
• 负责人: Geoffrey Dahl
• 金额: $ 13.84万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1247362&HistoricalAwards=false
• 关键词: RAPID; Elevated; Utero; Temperature; Suppressor

A series of studies using the bovine calf as a model was recently completed to exame the impact of in utero heat stress on ruminant fitness during the immediate post-natal period. The studies indicate that calves that experience in utero heat stress are smaller at birth and weaning, have reduced passive immune transfer, and depressed innate immune function. A project designed to further examine the health and performance of cows that experience heat stress during the final 60 days of gestation is currently underway. The availability of calves that experience in utero heat stress under such defined conditions during late gestation presents a unique opportunity to gain further insight into environmental factors that alter neonatal health and development, and possibly induce life-long differences in immune function that alter fitness. RAPID funding of this application is essential to capitalize on this unique opportunity to gain insight into the fundamental biology of heat stress. The first proposed objective is to tease apart the cellular mechanisms responsible for the observed differences in immunoglobulin uptake, and to determine if in utero and early-life differences in immune status persist in later life. Intestinal capacity for immunoglobulin absorption could be reduced by heat stress in utero. That hypothesis will be tested by measuring tissue and cellular levels of IgG absorption and relative levels of apoptosis in neonatal calves from dams that experience heat stress or cooling during late gestation. To more fully assess the long-term impact of in utero heat stress, functional immune endpoints and growth in calves from heat stressed and cooled dams will be compared. Immune suppression observed in heat-stressed cows and/or their calves may also result from differences in their immune cell subsets compared to those that are cooled. To address this possibility, peripheral blood of cows 8 weeks pre- and post-partum and peripheral blood, spleen and thymus of calves sacrificed to address the first objective above will be evaluated by flow cytometry for the frequency of different types of immune cells including B cells, T cells, monocytes, macrophages and granulocytes. A broad understanding of the cellular mechanisms of immune function following in utero heat stress, and the impact on growth and survival to puberty, as an indicator of overall fitness will therefore be developed as a result of this project. The broader impacts of the proposed study include enhanced understanding of heat stress biology, and the potential to develop management interventions for farmed and captive ruminants with improved capacity to thrive under higher ambient temperatures. To accomplish these goals, continued graduate educational support is necessary. There is also a need to expand the diversity of those trained in the field of animal biology to better represent the general population. Two outstanding young women scientists of Hispanic ethnicity will work on this project as graduate students. The University of Florida also has a significant population of undergraduate students of Hispanic descent and two of those students have been recruited to introduce them to basic research methods, techniques in immunology, and data summary and presentation. The undergraduates will assist with all aspects of the animal care, sample collection, and conduct of immune function assays. Thus the proposal will add significantly to the capacity and diversity of students trained in animal biology at the University of Florida.

最近完成了一系列以小牛为模型的研究，以探讨子宫内热应激对反刍动物出生后即刻健康的影响。研究表明，在子宫内经历热应激的小牛在出生和断奶时较小，被动免疫转移减少，先天免疫功能低下。目前正在进行一个项目，旨在进一步检查在妊娠最后60天期间经历热应激的奶牛的健康和性能。在妊娠后期，在这种特定条件下经历子宫内热应激的小牛的可用性提供了一个独特的机会，可以进一步了解改变新生儿健康和发育的环境因素，并可能诱导终身免疫功能差异，从而改变适应性。快速资助这一应用对于利用这一独特的机会深入了解热应激的基础生物学至关重要。第一个提出的目标是梳理除了负责观察到的免疫球蛋白摄取差异的细胞机制，并确定是否在子宫内和生命早期的免疫状态差异持续到以后的生活。子宫内热应激可降低肠道免疫球蛋白吸收能力。将通过测量来自妊娠后期经历热应激或降温的母鼠的新生小牛的IgG吸收的组织和细胞水平以及细胞凋亡的相对水平来检验该假设。为了更全面地评估宫内热应激的长期影响，将比较热应激和冷却母鼠的小牛的功能性免疫终点和生长。在热应激奶牛和/或其小牛中观察到的免疫抑制也可能是由于其免疫细胞亚群与冷却的免疫细胞亚群相比存在差异。为了解决这种可能性，将通过流式细胞术评价产前和产后8周奶牛的外周血以及为解决上述第一个目的而处死的小牛的外周血、脾脏和胸腺中不同类型免疫细胞（包括B细胞、T细胞、单核细胞、巨噬细胞和粒细胞）的频率。因此，作为该项目的结果，将对子宫内热应激后免疫功能的细胞机制以及对生长和青春期存活的影响进行广泛的了解，作为整体健康的指标。拟议研究的更广泛影响包括加强对热应激生物学的理解，以及为养殖和圈养反刍动物开发管理干预措施的潜力，这些反刍动物在更高的环境温度下茁壮成长的能力有所提高。为了实现这些目标，继续研究生教育的支持是必要的。 还需要扩大在动物生物学领域受过培训的人员的多样性，以更好地代表一般人口。两名西班牙裔杰出的年轻女科学家将作为研究生参与该项目。佛罗里达大学也有相当数量的西班牙裔本科生，其中两名学生被招募来向他们介绍基本的研究方法、免疫学技术以及数据总结和介绍。本科生将协助动物护理，样本收集和免疫功能测定的进行的各个方面。因此，该提案将显着提高佛罗里达大学动物生物学专业学生的能力和多样性。