Biology of early pregnancy in the mare

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Our research aims at understanding the interactions of the equine embryo with its environment in the mare's uterus during the first month of pregnancy, a time when 10-20% of pregnancies are lost for reasons that we do not understand. The success and failure of early pregnancy is of fundamental and economic importance in all the domestic animals but the horse is an especially good species in which to study its underlying physiopathology; the equine embryo can be flushed from the uterus throughout the second to fourth weeks without harming the mare and has structural and functional features that are not found in other species. One such feature is the embryo's production and use of steroid hormones that we believe to be very important in influencing its local environment. This 'steroidogenesis', steroid metabolism, and embryonic target cells are being studied in detail, paying particular attention to the possible role of estrogens in the development of the cardiovascular system. Another unusual feature is a thin, tough, transparent capsule that envelops the hollow ball of cells (the conceptus) as its diameter expands rapidly from less than 0.2 mm to more than 20 mm during its first two weeks in the uterus. Having described the more abundant biochemical components of the capsule and uterine secretions, we will now use more sensitive analytical methods to test our hypothesis that changes in the capsule allow the conceptus to be "fixed" and oriented where the placenta will later develop, and that alterations in released signalling molecules or nutrient transport are associated with pregnancy failure. To discover what goes wrong when pregnancy fails, we use a model system of 'compromised' pregnancy; during the third week of pregnancy we treat some mares with a prostaglandin that reduces progesterone production by the ovary. Despite the treatment, the conceptus can survive in the uterus for another 3-4 days after which it is recovered and compared with conceptuses from 'control', untreated mares. Comparisons of conceptuses and uterine materials from normal and compromised pregnancies are enabling us to pinpoint differences in proteins and steroid hormone activities that are associated with pregnancy failure.