Molecular Mechanisms of Parturition

描述（由申请人提供）：分娩，分娩的过程，是一种基本的生物学功能，其分子机制知之甚少。每年，全世界约有450万名严重早产儿由于无法正常分娩而出生，与过期妊娠分娩有关的并发症给母亲和婴儿造成无数问题。尽管对人类和其他物种的分娩进行了广泛的研究，但启动和终止这一过程的事件顺序仍然不清楚。 拟议的研究将使用分娩缺陷小鼠模型来定义伴随分娩开始和进展的分子事件。该模型具有破坏类固醇5 α还原酶基因的靶向突变（类固醇5 α还原酶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，以剖析野生型和5alphaR1KO雌性妊娠期间导致宫颈重塑的步骤。将开展研究，以确定通过cDNA微阵列基因芯片分析鉴定的新基因在宫颈成熟中的作用。5alphaR1基因在妊娠期间以组织和时间特异性模式表达。将启动研究，以确定控制女性生殖道中5alphaR1表达的调控序列。这些研究中应用的综合方法将为控制小鼠分娩的机制提供新的分子见解，并为人类分娩的长期研究建立遗传框架。

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.