Biology of early pregnancy in the mare

我们的研究旨在了解马胚胎在怀孕第一个月期间与母马子宫内环境的相互作用，在这段时间里，10%-20%的怀孕会因为我们不知道的原因而丢失。早期怀孕的成功和失败对所有家畜都具有根本和经济上的重要性，但马是研究其潜在生理病理的一个特别好的物种；马的胚胎可以在第二到第四周内从子宫中冲洗出来，而不会伤害母马，并且具有其他物种没有的结构和功能特征。其中一个特征是胚胎产生和使用类固醇激素，我们认为这种激素在影响当地环境方面非常重要。这种类固醇合成、类固醇代谢和胚胎靶细胞正在被详细研究，特别关注雌激素在心血管系统发育中的可能作用。另一个不同寻常的特征是一个薄薄、坚韧、透明的囊膜，包裹着中空的细胞球(胚胎)，在它进入子宫的头两周里，直径从不到0.2毫米迅速扩大到超过20毫米。在描述了包膜和子宫分泌物中更丰富的生化成分之后，我们现在将使用更灵敏的分析方法来检验我们的假设，即包膜中的变化可以使受孕“固定”并定位到后来胎盘发育的位置，以及释放的信号分子或营养运输的变化与妊娠失败有关。为了找出怀孕失败后的问题所在，我们使用了一个“受孕”的模型系统；在怀孕的第三周，我们给一些母马服用前列腺素，以减少卵巢产生的黄体酮。尽管进行了治疗，但受精卵还可以在子宫中存活3-4天，之后它会被恢复，并与未经处理的对照母马的受精卵进行比较。对正常妊娠和不良妊娠的胚胎和子宫材料进行比较，使我们能够准确地确定与妊娠失败有关的蛋白质和类固醇激素活动的差异。

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.