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.

Project Report

As global temperature rises there are profound impacts on agricultural productivity, yet concurrent population growth necessitates an increase in total food production. Indeed, it is predicted that total food production must increase by 50 to 70% by 2050 to meet anticipated demands of a population of 9 billion people, and much of that yield increase will result from technological advances in the agricultural sciences. Food production from ruminants is particularly important in developed and developing countries especially because of their ability to convert forage and byproduct resources that are unsuitable for human consumption to high value protein for human use. But heat stress during development may adversely affect fitness in after birth. Maternal heat stress during the late gestation affects calf health and immune response during postnatal life, but it is still unknown how in utero heat stress affects immune system development. Thus, the objective of this project was to evaluate the effects of in utero heat stress on distribution of different immune cell types in blood and primary and secondary lymphoid tissues of the calf. In addition, we sought to determine if the relatively brief insult of heats stress for the final 6 weeks of gestation would affect future productive and reproductive fitness of the calf as an adult. We monitored early postnatal immune function in calves and observed a decrease in thymus weight in calves that experienced heat stress in utero, and heat stress induced shifts in the lymphocyte population of the spleen, increasing the proportion of B cells. Thus, heat stress reduced immune fitness in early life. Calves that were heat stressed for the final 6 weeks in gestation were smaller at birth and never achieved the same weight as their cooled herdmates up to one year of life, and were more likely to leave the herd due to disease. At maturity, the calves heat stressed in utero had reduced reproductive fitness and lagged in lactational output relative to their cooled herdmates. These data suggest that heat stress during the last 6 weeks of gestation negatively immune system development and lymphoid tissue maturation in the neonate. Further, in utero heat stress impacts fertility and milk production up to and through the first lactation of offspring. This is, to our knowledge, the first time that an in utero insult as a result of normal climate variation has been shown to impact fitness variables in the adult. The results offer a potential model to study the impact of a climate variable on epigenetic mechanisms that alter fitness and performance. The model has relevance to agricultural production, but also to consideration of adaptive mechanisms in wild ruminants as they are also subject to greater heat stress as the planet warms.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Type
Standard Grant (Standard)
Application #
1247362
Program Officer
Steven Ellis
Project Start
Project End
Budget Start
2012-07-15
Budget End
2014-06-30
Support Year
Fiscal Year
2012
Total Cost
$138,386
Indirect Cost
Name
University of Florida
Department
Type
DUNS #
City
Gainesville
State
FL
Country
United States
Zip Code
32611