INHIBITION OF UTERINE CONTRACTIONS BY FETAL MEMBRANES

这项建议的目的是研究人胎膜的作用。 抑制系统在控制子宫收缩中的作用 理解启动过程中涉及的基本机制的术语目标 劳动力的问题。维持子宫安静的生物学机制 在怀孕的大部分时间里，并导致足月过渡到分娩 不是很清楚。胎膜、羊膜和绒毛膜，以及 母体蜕膜被认为在旁分泌信号中起重要作用。 控制子宫收缩、宫颈扩张和生育。这个 胎膜位于胎儿和母体蜕膜之间， 子宫肌肉。因此，它们处于规范信号传递的理想位置 分娩时母亲和胎儿之间的距离。过去的研究 许多研究人员的努力集中在子宫刺激因子上 从胎膜中释放的宫缩。最近，我们开发了一种双重的 房室-胎膜-子宫肌体外模型的研究 胎膜、母体蜕膜和子宫肌的相互作用。在……里面 在这个系统中，胎膜被密封在有机玻璃腔中，以便 每个半室都是胎儿或母体一侧的隔间。 母体一侧增加一条子宫肌条。因此， 子宫上的胎膜可以通过测量直接评估 子宫收缩的变化。系统的所有组件，胎儿 胎膜、母体侧信号和子宫肌肉模型可以 在这个体外系统中很容易操作。在最近出版的著作中，我们 意外发现人足月分娩的胎膜抑制 自发性子宫收缩，这种抑制是可逆的 这种抑制作用是绒毛膜/蜕膜侧面特有的 因为羊膜面朝向肌肉的膜不会 表现出抑制。这改变了我们研究的重点，从 对胎膜中存在的抑制系统有刺激作用。 此外，该提案中显示的初步数据表明， 胎膜因子能抑制BAY K8644(一种L型钙离子 通道激动剂)引起的子宫收缩。这些数据导致了 提出的假设是胎膜抑制物是一种内源性 钙通道拮抗剂。胎膜抑制物质有 在分娩开始以及分娩过程中作为重要调节器的潜力 在临产治疗中作为新疗法的潜力 早产等异常现象。这份修订后的第一笔拨款申请 提出了一系列实验，为 胎膜因子作为内源性钙通道抑制因子，以及 确定胎膜抑制物在胎盘早破发病中的意义 劳力。

The purpose of this proposal is to study the role of human fetal membrane inhibitory systems in the control of uterine contractions with the long term goal of understanding the basic mechanisms involved in the initiation of labor. The biological mechanisms that maintain uterine quiicscence throughout most of pregnancy and cause the transition to labor at term are not clearly understood. The fetal membranes, the amjiion and chorion, and the maternal decidua are thought to be important in paracrine signalling and control of uterine contractions, cervical dilation and birth. The fetal membranes are interposed between the fetus and maternal decidua and uterine muscle. Thus, they are ideally positioned to regulate signal1ing between mother and fetus at the time of initiation of labor. Past research efforts by many investigators focused on stimulators of uterine contractions released from fetal membranes. Recently, we developed a dual chamber-fetal membrane-uterine muscle in vitro model to study the interactions of fetal membranes, maternal decidua and uterine muscle. In this system, fetal membranes are sealed into a Plexiglass chamber so that each hemichamber is a compartment for either the fetal or maternal side. A uterine muscle strip is added to the maternal side. Thus, effects of fetal membranes on the uterus can be assessed directly by measuring changes in uterine contractions. All components of the system, fetal membranes, maternal side signals and the uterine muscle model can be easily manipulated in this in vitro system. In recently published work, we unexpectedly found that human, term, labored fetal membranes inhibit spontaneous uterine contractions, that this inhibition is reversible and that the inhibitory effect is specific to the chorion/decidual side because membranes mounted with the amnion side toward the muscle did not show inhibition. This has changed the focus of our research efforts from stimulatory to inhibitory systems which are present in fetal membranes. Furthermore, preliminary data shown in this proposal suggests that the fetal membrane factor is able to inhibit BAY K8644 (a L-type calcium channel agonist) induced uterine contractions. These data lead to the proposed hypothesis that the fetal membrane inhibitor is an endogenous calcium channel antagonist. Fetal membrane inhibitory substances have potential as important regulators in the initiation of labor as well as potential as new therapies in the treatment of labor initiation abnormalities such as preterm labor. This revised FIRST grant application proposes a series of experiments to assign a mechanism of action for the fetal membrane factor as an endogenous calcium channel inhibitor, and establish the significance of the fetal membrane inhibitor to the onset of labor.