AGING EFFECTS ON TRANSVAGINAL TRANSPORT

描述：我们广泛的、长期的目标是了解 调节女性体内液体和溶质运动的机制 生殖道上皮。我们目前研究的主要目标是 了解女性年龄增长如何导致宫颈分泌物减少 粘液和阴道液。我们将利用PI拥有的一种新方法 用于培养人宫颈和宫颈/阴道上皮细胞 关于过滤器，我们建议检验四个假设：a.老化是 与宫颈细胞旁通透性降低有关 阴道上皮细胞运输液体和溶质，从而导致 体液分泌减少。B.衰老改变了稳定状态 宫颈和阴道上皮细胞中作用丝的平衡 宫颈和阴道上皮细胞中的F-肌动蛋白细丝向 宫颈和阴道上皮细胞中的F-肌动蛋白细丝朝向F-肌动蛋白 宫颈和阴道上皮细胞中的纤维朝向F-肌动蛋白； 产生一种坚硬的细胞骨架，不允许细胞收缩 以响应刺激并增加细胞间质的体积 空间，这，降低了细胞旁的渗透性。雌激素，在 与衰老相反，将平衡转移到G-肌动蛋白，从而产生 一种更具活力的细胞骨架。C.人类宫颈和阴道细胞 产生一氧化氮(NO)，而NO能抑制肌动蛋白聚合 并增加细胞旁通透性。D.在人类的颈部和 阴道细胞，雌激素通过上调NO的生成来增加NO的产生 钙依赖性一氧化氮合酶(EcNOS)。方法将包括助熔剂和 在改良的扩散/使用室中进行骨的电生理学研究， 贴壁细胞的荧光显微镜用于测定细胞的变化 贴壁细胞的细胞大小、生化和分子生物学显微镜 用于细胞ZIE、生化和分子变化的测定 生物化验。这项研究可能会提供关于年龄和 雌激素对宫颈和阴道细胞功能的影响。健康状况 项目的关联性：在本研究中获得的知识可能是 对了解宫颈疾病的发病机制很重要。 不孕不育(“宫颈因素”)以及过度或减少的情况 宫颈粘液和阴道液的分泌物。了解机制 调节宫颈粘液的产生对于发育是重要的 改变宫颈粘液特性的化合物。这些数据可能会改善 我们对绝经后妇女雌激素替代的认识。他们 还可以通过以下方式提供高效和简单的节育方法 以已知的宫内传播和转运机制为目标。

DESCRIPTION: Our broad, long-term objective is to understand the mechanisms that regulate movement of fluid and solutes across the woman's reproductive tract epithelium. Our main objective in the present study is to understand how aging in women leads to decreased production of cervical mucus and vaginal fluid. We will utilize a new method that the PI has developed to culture human cervical and cervico/vaginal epithelial cells on filters, and we propose to test four hypotheses: A. That aging is associated with decreased paracellular permeability of the cervical and vaginal epithelia to transport of fluids and solutes, which leads to decreased fluid secretion. B. That aging shifts the steady-state equilibrium of action filaments in cervical and vaginal epithelial cells towards F-actin filaments in cervical and vaginal epithelial cells towards F-actin filaments in cervical and vaginal epithelial cells towards F-actin filaments in cervical and vaginal epithelial cells towards F-actin; this produces a rigid cytoskeleton which does not allow the cells to contract in response to stimuli and to increase the volume of the intercellular space, this, decreasing the paracellular permeability. Estrogen, in contrast to aging, shifts the equilibrium towards G-actin, thus producing a more dynamic cytoskeleton. C. That human cervical and vaginal cells produce nitric oxide (NO), and that NO can inhibit actin polymerization and increase paracellular permeability. D. That in human cervical and vaginal cells, estrogen increase production of NO by up-regulation of calcium-dependent NO-synthase(ecNOS). Methods will include flux and electrophysiological studies bone in a modified diffusion/Ussing chamber, fluorescence microscopy of attached cells for determinations of changes in cell size, biochemical and molecular biology microscopy of attached cells for determinations of changes in cell zie, biochemical and molecular biology assays. The present study may provide novel information on age-and estrogen-related effects on cervical-and vaginal-cell function. Health relatedness of the project: the knowledge gained in present study may be important for understanding mechanisms of disease in the cervix e.g. infertility ("cervical factor"), and conditions of excessive or diminished secretion of cervical mucus and vaginal fluid. Understanding mechanisms and regulation of cervical mucus production is important for developing compounds to alter cervical mucus characteristics. These data may improve our understanding of estrogen replacement to postmenopausal women. They may also provide efficient and simple modalities for birth control by targeting known mechanisms of transcervical and transport.