Biology of early pregnancy in the mare

我们的研究旨在了解怀孕第一个月期间马胚胎与母马子宫内环境的相互作用，此时10-20%的妊娠因我们不了解的原因而丢失。早期妊娠的成功和失败对所有家畜都具有重要的基础和经济意义，但马是研究其潜在生理病理学的特别好的物种;马胚胎可以在第二至第四周从子宫中冲洗出来，而不会伤害母马，并且具有其他物种所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，我们认为这对影响其局部环境非常重要。正在详细研究这种“类固醇生成”、类固醇代谢和胚胎靶细胞，特别关注雌激素在心血管系统发育中的可能作用。另一个不寻常的特征是一个薄，坚韧，透明的胶囊，包裹着中空的细胞球（孕体），因为它的直径在子宫内的前两周内迅速从不到0.2 mm扩大到超过20 mm。在描述了包膜和子宫分泌物中更丰富的生化成分后，我们现在将使用更灵敏的分析方法来检验我们的假设，即包膜的变化允许孕体被“固定”并定位在胎盘随后发育的位置，并且释放的信号分子或营养物质转运的改变与妊娠失败有关。为了发现怀孕失败时出现的问题，我们使用了一个“妥协”怀孕的模型系统;在怀孕的第三周，我们用前列腺素治疗一些卵巢，减少卵巢孕酮的产生。尽管进行了治疗，但孕体仍能在子宫内存活3-4天，然后恢复，并与“对照”、未治疗的子宫内孕体进行比较。比较正常妊娠和受损妊娠的孕体和子宫材料，使我们能够确定与妊娠失败相关的蛋白质和类固醇激素活性的差异。

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.