-Dr. Douglas F. Antczak
Dr. Douglas F. Antczak
One key application of the recently sequenced equine genome is the use of global gene expression microarrays to determine the relative activity of most or all of the estimated 20,000+ genes in the equine genome in single experiments that compare normal and disease states, or responses to different therapeutic treatments. In the coming two years we propose to study aspects of early placental development in the mare using a new expression microarray that our laboratory has produced and validated over the past 6 months. The preliminary data from our pilot experiments indicate that the new expression array is highly sensitive and reproducible. Moreover, it includes over 14,000 of the estimated 20,000 + horse genes, and therefore allows detection of virtually all of the major molecular pathways involved in normal growth, function, and pathology. We are making this new array available to equine scientists worldwide, and it is already being used by other equine researchers at Cornell.
We will use the expression microarray to test the hypothesis that the trophoblast cells of the equine chorionic girdle express many genes associated with tumor invasion and immune regulation. We propose that these genes permit the chorionic girdle cells to migrate from the developing equine placenta into the endometrium of the mare, where they evade maternal immune responses during their three month lifespan. These cells are the source of the hormone Equine Chorionic Gonadotrophin that plays a critical role in the maintenance of early pregnancy. In year two we would compare gene expression in placental tissues from normal equine pregnancy with pregnancies that are failing near the time of chorionic girdle invasion, and also examine gene expression in the endometrium using the same microarray assay to determine how the uterus prepares for normal placental invasion, and how it might change in failing pregnancy. We would also determine the global gene expression patterns of lymphocytes from around the endometrial cups and compare them to peripheral blood lymphocytes from pregnant and non-pregnant mares. This research will contribute to our understanding of normal and abnormal equine pregnancy.