MECHANISMS OF LUMINAL ACIDIFICATION IN EPIDYDIMAS & VAS DEFERENS

附睾管腔酸化机制

• 批准号: 7953821
• 负责人: SYLVIE BRETON
• 金额: $ 0.56万
• 依托单位: MARINE BIOLOGICAL LABORATORY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953821
• 关键词: Bicarbonates; Cell membrane; Clear Cell; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Duct (organ) structure; Electrodes; Environment; Enzymes; Epididymis; Epithelial Cells; Fertility; Funding; Goals; Grant; Institution; Intervention; Laboratories; Organ; Pathologic; Prevention; Process; Proton Pump; Proton-Translocating ATPases; Protons; Recycling; Regulation; Reproductive Physiology; Research; Research Personnel; Resources; Source; Sperm Maturation; United States National Institutes of Health; Vas deferens structure; Vesicle; apical membrane; male; premature; reproductive; reproductive function; sperm cell

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Active proton transport mechanisms establish and maintain a luminal acidic environment in the excurrent ducts of the male reproductive tract. The low luminal pH and a low bicarbonate concentration are important for sperm maturation, the prevention of premature activation of acrosomal enzymes, and for maintaining sperm in a quiescent state during storage in this organ. Despite this critical function in male reproductive physiology, acidification processes in the male reproductive tract are still incompletely understood. Our laboratory is studying the mechanisms that participate in luminal acidification and its regulation in the epididymis and vas deferens. The ultimate goals of this study are to understand how defective acidification may impair reproductive function in pathologic states, and how intervention to manipulate acidification may eventually be used to control male fertility. The non-invasive self-referencing proton-selective micro electrode developed in the BioCurrrents Research Center has allowed us to identify the major proton secretory mechanism in the initial part of the vas deferens. In collaboration with Peter Smith, we have shown that a bafilomycin-sensitive, vacuolar proton-pumping H+-ATPase (V-ATPase) is concentrated in the apical membrane of a subpopulation of epithelial cells (clear cells) and is a major contributor to luminal acidification. In acidifying clear cells, proton secretion is regulated via recycling of V-ATPase-containing vesicles to and from the plasma membrane. .

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 主动的质子运输机制在男性生殖道的流出管道中建立和维持一个流明的酸性环境。低的管腔pH和低的碳酸氢盐浓度对于精子成熟、防止顶体酶的过早激活以及在该器官储存期间保持精子的静止状态是非常重要的。尽管这在男性生殖生理学中起着关键作用，但男性生殖道中的酸化过程仍然不完全清楚。本实验室正在研究附精和输精管腔内酸化的参与机制及其调节。这项研究的最终目标是了解酸化缺陷如何在病理状态下损害生殖功能，以及如何最终使用干预酸化来控制男性生育能力。 生物电流研究中心研制的无创自参照式质子选择微电极使我们能够识别输精管起始部的主要质子分泌机制。在与Peter Smith的合作中，我们已经证明了巴非霉素敏感的液泡质子泵H+-ATPase(V-ATPase)集中在一组上皮细胞(透明细胞)的顶膜上，是腔内酸化的主要贡献者。在酸化的透明细胞中，质子的分泌是通过含有V-ATPase的囊泡循环到质膜和从质膜循环来调节的。 。