Crosstalk between metabolic and signaling pathways involved in sperm capacitation

精子获能涉及的代谢和信号通路之间的串扰

• 批准号: 10170392
• 负责人: JOCHEN BUCK
• 金额: $ 47.54万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-21 至 2022-09-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170392
• 关键词: ATP Synthesis Pathway; Acrosome Reaction; Adenylate Cyclase; Bicarbonates; Biochemical; Bioenergetics; Buffers; Carbon Dioxide; Cells; Citric Acid Cycle; Consumption; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Data; Ejaculation; Enzymes; Epididymis; Equilibrium; Event; Fertilization; Fibroblasts; Glucose; Glycolysis; Human; In Vitro; Incubated; Infertility; Investigation; Knock-out; Knockout Mice; Knowledge; Liquid substance; Mammalian Oviducts; Mediating; Metabolic; Metabolic Pathway; Metabolism; Mitochondria; Mitochondrial Matrix; Modernization; Molecular; Mus; Nutrient; Operative Surgical Procedures; Oxidative Phosphorylation; Pathway interactions; Patients; Pattern; Pharmacology; Physiological; Physiology; Process; Production; Regulation; Role; Seminal Plasma; Signal Pathway; Somatic Cell; Sperm Capacitation; Sperm Motility; Swimming; Testing; cell motility; cell type; contraceptive target; egg; glucose uptake; high energy compound; improved; inhibitor/antagonist; metabolomics; mouse model; novel; reproductive tract; response; sensor; sperm cell; zygote

Summary/Abstract (no more than 30 lines) Mammalian sperm acquire fertilization capacity as they transit through the reproductive tract in a process known as capacitation. During capacitation, sperm change their motility pattern and become competent to undergo an acrosome reaction and fertilize an egg. Capacitation-associated processes require energy. Similar to somatic cells, sperm generate ATP and other high energy compounds using nutrients in their surroundings via the coordinated actions of numerous metabolic pathways, including glycolysis and mitochondrial oxidative phosphorylation. In sperm, it remains unclear how these pathways are coordinately regulated to generate sufficient energy for motility and capacitation. In this application, we propose to apply modern metabolite profiling combined with metabolic flux analysis to sperm physiology to identify the contributions of the different metabolic pathways used by sperm. These studies will test the central hypothesis that sperm actively up-regulate their metabolism during capacitation to generate sufficient energy for motility and other capacitation- associated processes necessary for fertilization. Soluble adenylyl cyclase (sAC) is essential for the molecular changes observed during capacitation. In other contexts, sAC is a metabolic sensor. Therefore, we will also test the hypothesis that sAC acts as a metabolic sensor in sperm which regulates the metabolic changes induced by capacitation, and regulates energy production during sustained sperm motility. !

摘要/摘要（不超过 30 行） 哺乳动物的精子在通过精子时获得受精能力 生殖道的过程称为获能。在获能过程中，精子 改变他们的运动模式并有能力经历顶体 反应并使卵子受精。与获能相关的过程需要能量。 与体细胞类似，精子产生 ATP 和其他高能化合物 通过众多个体的协调行动来利用周围环境中的营养物质 代谢途径，包括糖酵解和线粒体氧化 磷酸化。在精子中，这些途径如何运作仍不清楚 协调调节以产生足够的能量用于运动和获能。 在此应用中，我们建议应用现代代谢物分析结合 通过对精子生理学的代谢通量分析来确定 精子使用的不同代谢途径。这些研究将测试 中心假设是精子在过程中积极上调其新陈代谢 产生足够能量用于运动和其他能力的能力 受精所需的相关过程。可溶性腺苷酸环化酶 (sAC) 对于获能过程中观察到的分子变化至关重要。在其他方面 在上下文中，sAC 是一种代谢传感器。因此，我们还将检验假设 sAC 作为精子中的代谢传感器，调节代谢 能力引起的变化，并调节能量产生 持续的精子活力。 ！