早产是新生儿死亡的首要原因，阐明人类分娩机制是有效防治早产的重要前提。孕激素是维持妊娠的主要激素，但人类妊娠晚期母血孕激素水平并未下降，因此研究分娩启动中孕激素功能性撤退的机制具有临床意义。胎膜是分娩启动信号的重要来源，由其再生的糖皮质激素促进胎膜前列腺素合成是分娩启动关键事件之一，但孕激素却制约糖皮质激素这一促分娩作用的发挥。我们预实验发现糖皮质激素通过上调胎膜孕激素代谢酶AKR1C1表达的方式制约孕激素的作用从而导致胎膜孕激素功能性撤退。本项目我们将夯实糖皮质激素诱导的胎膜AKR1C1在分娩启动中的作用并探讨其机制，为早产防治提供新思路。

Preterm birth is the leading cause of neonatal death. To prevent and combat preterm birth effectively, it is crucial to elucidate the mechanisms which lead to human parturition. Progesterone plays a dominant role in the maintenance of pregnancy. However, a decline in circulating progesterone levels does not occur prior to parturition in humans. Therefore, it is of clinical significance to understand the functional withdrawal of progesterone in late gestation. Fetal membranes contribute triggering signals for parturition and the up-regulation of prostaglandins synthesis by glucocorticoids regenerated in the fetal membranes is one of crucial events in the initiation of labor, which is attenuated by progesterone during gestation. Our preliminary study showed that glucocorticoids might induce the functional withdrawal of progesterone by up-regulating the expression of AKR1C1, an enzyme associated with progesterone metabolism, in the fetal membranes. In this proposed study, we will further validate the role of glucocorticoid-induced AKR1C1 expression in the functional withdrawal of progesterone in the fetal membranes in human parturition and investigate the underlying mechanisms with an aim to develop novel strategies for the prevention of preterm birth.