Maternal immune function during pregnancy can profoundly influence embryonic development. The prevalence of preterm births due to uterine infection, the transmission of infectious disease from mother to fetus, and the possibility of immunologically-based miscarriage in humans all highlight the importance of understanding how the maternal immune system influences fetal health and development. Recent progress has been made toward understanding the effect of maternal immune stimulation on pregnancy outcome, and mouse models offer some insight into how this influence may play out at the uterine interface between mother and fetus. Because the local interactions between mother and fetus in the uterus are inaccessible in humans, the choice of an appropnate model system is important. In an outbred rat model, it is possible to look directly at how the mother's immune system influences events in the uterus during embryo development and also assess how particular genetic differences between the mother and embryo may adjust the action of immune system.
The specific aims of this research are threefold. First, we will characterize the effect of maternal immunostimulation on embryo and placental development in the rat. Second, we will develop a DNA-based technique to determine the Major Hisrocompatibility Complex (MHC) haplotype of outbred Sprague-Dawley rats. Third. we will use this technique to assess the role of MHC sharing between mother and embryo on pregnancy outcome and immune cell infiltration of the uterus during pregnancy. Together, the completion of these specific aims will clarify the role the maternal immune system plays in pregnancy and pregnancy loss in the rat, and illuminate some of the ways in which embryonic genotype may modify the mother's response.
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