HUMAN DECIDUA AND FETAL MEMBRANES AS A PARACRINE SYSTEM

人类蜕膜和胎膜作为旁分泌系统

• 批准号: 3324809
• 负责人: Gillian Doreen Bryant-Greenwood
• 金额: $ 13.78万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3324809
• 关键词: RNase protection assay; amnion; autoradiography; birth; chorioallantoic membrane; collagenase; decidua; embryo /fetus membrane; endometrium; enzyme inhibitors; extracellular matrix; gene expression; hormone receptor; hormone regulation /control mechanism; human tissue; immunocytochemistry; in situ hybridization; messenger RNA; northern blottings; paracrine; placenta; plasminogen activator; proteolysis; relaxin; secretion; tissue /cell culture

The potential of the human decidua/fetal membrane system as an accessible autocrine/paracrine model will be further explored, in order to elucidate the role of relaxins in the local control of collagenolysis and the rupture of the fetal membranes at parturition. An added challenge is our finding that the second human relaxin gene (H1) is expressed in this system. This will be accomplished by studying the four components of the relaxin system: gene expression, control of secretion, biological effects and receptor distribution. Relaxin H1 and H2 gene expression and the translated products, will be identified in the endometrium/decidua, fetal membranes and placenta with specific riboprobes and antibodies throughout the cycle and pregnancy. The effect on decidual cell relaxin secretion and the mRNA levels for relaxins by a range of decidual and placental hormones will be studied in in vitro. The biological effects of human relaxin H2 on fetal membrane/decidual production of key collagenolytic enzymes and inhibitors will be sought both in vitro and in vivo. Changes in the concentration of relaxin receptors in intrauterine tissues will be studied through the cycle and gestation by quantitative autoradiography and the results related to those from the experiments above. The combined results will provide insights into significant problems, the local control of the accommodation of the fetal membranes to the growing fetus in the last weeks of pregnancy, and the timing of normal spontaneous membrane rupture. These studies will lead to a greater understanding of premature rupture of the fetal membranes, a major cause of premature birth which results in infants with a high incidence of neurodevelopmental impairment.

人类蜕膜/胎膜系统作为一种可及的 自分泌/旁分泌模型将进一步探讨，以阐明 松弛素在局部控制胶原溶解和破裂中的作用 在分娩时的胎膜。 另一个挑战是我们发现 第二个人松弛素基因（H1）在该系统中表达。 这将通过研究松弛素的四种成分来实现 系统：基因表达、分泌控制、生物学效应和 受体分布 松弛素H1和H2基因表达和翻译产物，将被 在子宫内膜/蜕膜、胎膜和胎盘中发现， 特异性核糖核酸探针和抗体在整个周期和怀孕。 不同浓度地塞米松对蜕膜细胞松弛素分泌及mRNA水平的影响 将研究一系列蜕膜和胎盘激素的松弛作用， 体外 人松弛素H2对胎膜/蜕膜的生物学效应 将寻求关键的胶原蛋白溶解酶和抑制剂的生产， 在体外和体内。 子宫内组织松弛素受体浓度的变化 将通过定量的周期和酝酿进行研究， 放射自显影及与实验相关的结果 以上 综合结果将提供对重大问题的见解， 局部控制胎膜对生长的适应 胎儿在怀孕的最后几周，和正常自发的时间 膜破裂 这些研究将使人们更好地了解 胎膜早破是早产的主要原因 这导致婴儿的神经发育 损伤