胎膜早破是导致早产的重要原因，但发生机制目前尚未完全阐明。我们以往发现妊娠晚期胎膜表达大量再生皮质醇的酶11b-HSD1，由此产生的皮质醇对胎膜11b-HSD1和前列腺素E2的合成都具有促进作用，从而形成胎膜糖皮质激素和前列腺素生成的正反馈机制，此正反馈机制是否还具有其它重要功能目前还不清楚。赖氨酰氧化酶是交联胶原蛋白抵抗胶原酶水解从而维持胎膜韧性的重要分子，胎膜的多种细胞都表达赖氨酰氧化酶，而且随孕期显著下降，我们认为此下降很可能与胎膜糖皮质激素和前列腺素生成的正反馈机制有关。我们预实验发现皮质醇和前列腺素E2对人羊膜成纤维细胞赖氨酰氧化酶的表达都有抑制作用，说明此设想基本成立。本课题我们将深入研究11b-HSD1、皮质醇和前列腺素E2在调控胎膜赖氨酰氧化酶表达中的相互关系，此原创性研究可以帮助我们从全新的视角诠释妊娠晚期胎膜皮质醇-前列腺素生成正反馈机制的生理意义和胎膜早破的机制。

Our previous studies have demonstrated that human fetal membranes express a large amount of 11beta-HSD1 which regenerates biological active cortisol at the end of gestation. Cortisol derived from this source exert feedforward induction of 11beta-HSD1 and prostaglandin synthesizing enzymes in the fetal membranes. Prostaglandin E2 derived from this positive feedback loop have been suggested to play an anti-tocolytic role in parturition. However whether this positive feedback loop plays other prominent roles in the fetal membranes is not known. Premature rupture of the fetal membranes (PROM) is one of the major cause of preterm labor and the mechanism underlying PROM is not very well understood. .Lysyl oxidase catalyzes the reactions that cross-link collagens thus stabilizing and strengthening the membranes. Lysyl oxidase is expressed in a variety of cells in the fetal membranes. Our preliminary study has shown that both cortisol and prostaglandin E2 inhibit lysyl oxidase expression in the amnion fibrobloasts, an important source of cortisol, prostaglandin E2 as well as collagen and lysyl oxidase in the fetal membranes. These findings are important original discovery of the novel role of this positive feedback loop of cortisol regeneration and prostaglandin E2 production in the fetal membranes. In this proposed study we will further investigate the effects of 11b-HSD1, cortisol and prostaglandin E2 on the expression of lysyl oxidase in the fetal membranes. The successful carry-out of this study will unveil the novel mechanism underlying PROM, which would implicate in the prevention of PROM and preterm labor.