Comparative studies on the regulation of metabolism during sperm capacitation

精子获能过程中代谢调节的比较研究

• 批准号: 10608684
• 负责人: JOCHEN BUCK
• 金额: $ 74.68万
• 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 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608684
• 关键词: Acrosome Reaction; Adenylate Cyclase; Adult; Assisted Reproductive Technology; Award; Bicarbonates; Bioenergetics; Cells; Citric Acid Cycle; Comparative Study; Consumption; Cyclic AMP; Data; Ejaculation; Embryonic Development; Energy-Generating Resources; Environment; Enzymes; Epididymis; Exposure to; Extracellular Fluid; Fatty Acids; Female; Fertilization; Fertilization in Vitro; Fructose; Funding; Genetic; Glucose; Glycolysis; Goals; Human; Image; Label; Liquid substance; Mammalian Oviducts; Mediating; Metabolic; Metabolic Pathway; Metabolism; Methodology; Mitochondria; Modernization; Molecular; Mus; Nutrient; Oocytes; Oxidative Phosphorylation; Pathway interactions; Pattern; Pentosephosphate Pathway; Pharmacology; Physiology; Process; Protein Isoforms; Pyruvate; Regulation; Reproduction; Resources; Second Messenger Systems; Seminal fluid; Signal Pathway; Signal Transduction; Site; Source; Sperm Capacitation; Swimming; Testing; Travel; cell motility; egg; in vitro activity; meetings; metabolomics; reproductive tract; response; sperm cell; sperm function; stable isotope; tool; zygote

Summary/Abstract 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 oocyte. These capacitation-associated processes require energy, and sperm are dependent on nutrients in their environment to complete them. Sperm are exposed to different nutrients in their surroundings as they pass from being stored in the cauda epididymis to the fallopian tube where they will meet and fertilize the oocyte. In the previous funding period, we demonstrated that sperm supplied with exogenous glucose generate ATP via glycolysis and oxidative phosphorylation, and glucose utilization via both pathways increases in capacitating sperm. In addition, we found that capacitating sperm alter activity through the pentose phosphate pathway and sperm deprived of exogenous nutrients can metabolize endogenous energy sources. We now propose to apply modern metabolite profiling combined with metabolic flux analyses to identify how sperm coordinately regulate their metabolic pathways and leverage different exogenous nutrients as they mature through distinct activation states. Soluble adenylyl cyclase (sAC) is essential for the molecular changes observed during capacitation, and we will use our unique tools for modulating its activity to test the hypothesis that sAC regulates the metabolic changes induced by capacitation.

摘要/摘要 哺乳动物的精子在通过卵母细胞时获得受精能力。 生殖道的一个被称为获能的过程。在获能过程中，精子 改变它们的运动模式，变得有能力经历顶体 反应并使卵母细胞受精这些与能力建设相关的进程需要 能量，精子依赖于环境中的营养物质来完成 他们精子在通过时会接触到周围环境中不同的营养物质 从储存在附睾尾到输卵管， 使卵母细胞受精在上一个融资期，我们证明， 外源性葡萄糖供精通过糖酵解和氧化作用产生ATP 磷酸化和葡萄糖利用通过这两种途径增加， 使精子获能此外，我们发现，获能精子改变活动， 通过戊糖磷酸途径和精子剥夺外源性 营养素可以代谢内源能量来源。我们现在建议 现代代谢物分析与代谢通量分析相结合， 精子协调地调节它们的代谢途径， 外源营养素，因为它们通过不同的激活状态成熟。可溶性 腺苷酸环化酶（sAC）是必不可少的分子变化观察期间 能力，我们将使用我们独特的工具来调节其活动，以测试 假设sAC调节获能诱导的代谢变化。