Molecular Mechanisms of Parturition

分娩的分子机制

• 批准号: 6765904
• 负责人: MALA S. MAHENDROO
• 金额: $ 28.08万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6765904
• 关键词: birth; cell differentiation; cell migration; cervix; clinical research; complementary DNA; extracellular matrix; female; gel mobility shift assay; gene expression; genetic regulation; genetically modified animals; human subject; human tissue; immunocytochemistry; in situ hybridization; inflammation; laboratory mouse; macrophage; microarray technology; neutrophil; steroid hormone metabolism; testosterone 5 alpha reductase; tight junctions; tissue /cell culture

DESCRIPTION (provided by applicant): Parturition, the process of giving birth, is an essential biological function for which the molecular mechanisms are poorly understood. Each year, some 4.5 million severely premature infants are born worldwide due to the failure of normal parturition, and complications associated with delivery in post-term pregnancies cause innumerable problems in both mother and child. Despite extensive studies examining parturition in the human and other species, the sequence of events that initiate and terminate this process remains unclear. The proposed studies will use a parturition defective mouse model to define molecular events that accompany initiation and progression of labor. This model has a targeted mutation that disrupts the steroid 5alpha reductase gene (Steroid 5alpha-reductase type 1 knockout: 5alphaR1KO). The 5alphaR1KO mice have a defect in cervical ripening. Physiological and molecular studies will be undertaken to dissect the steps leading to cervical remodeling during gestation in wild type and 5alphaR1KO females. Studies will be initiated to define the role of new genes in cervical ripening identified by cDNA micro-array gene chip analysis. The 5alphaR1 gene is expressed in a tissue and temporal specific pattern during pregnancy. Studies to identify the regulatory sequences controlling 5alphaR1 expression in the female reproductive tract will be initiated. The integrated approaches applied in these studies will provide novel molecular insight into the mechanisms controlling parturition in the mouse and establish a genetic framework for long-term studies in human parturition.

描述（由申请人提供）：分娩的过程是分子机制的重要生物学功能。每年，由于正常的分娩失败，全世界大约有450万个过早的婴儿出生，并且与后妊娠的分娩有关的并发症会导致母亲和儿童无数问题。尽管进行了广泛的研究，研究了人类和其他物种中的分娩，但启动和终止该过程的事件的顺序尚不清楚。 拟议的研究将使用分娩有缺陷的小鼠模型来定义伴随劳动启动和进展的分子事件。该模型具有靶向突变，可破坏类固醇5alpha还原酶基因（类固醇5alpha-reductase 1型敲除：5alphar1ko）。 5alphar1ko小鼠在宫颈成熟方面存在缺陷。 将进行生理和分子研究，以剖析导致野生型和5alphar1ko女性妊娠期间宫颈重塑的步骤。将开始研究以定义新基因在通过cDNA微阵列基因芯片分析鉴定的宫颈成熟中的作用。 5alphar1基因在怀孕期间以组织和时间特异性表达。将开始识别控制女性生殖道中5alphar1表达的调节序列的研究。这些研究中采用的综合方法将为控制小鼠的分娩机制提供新的分子见解，并为人类分娩中的长期研究建立遗传框架。