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

基本信息

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
项目类别：
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

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

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项目摘要

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在称为电容的过程中生殖道。在电容期间，精子改变其运动模式，并有能力参加Acrosome 反应并施肥卵母细胞。这些相关的过程需要能量，精子取决于其环境中的营养他们。精子通过时会在周围的不同营养从存储在cauda附睾到输卵管，他们将在那里见面并施肥卵母细胞。在上一个资金期间，我们证明了外源葡萄糖提供的精子通过糖酵解和氧化产生ATP 磷酸化和通过两种途径的葡萄糖利用都增加电容精子。此外，我们发现精子改变活性通过五磷酸五磷酸途径和被剥夺外源的精子营养可以代谢内源能源。我们现在建议申请现代代谢物谱分析与代谢通量分析相结合，以确定如何精子协调调节其代谢途径并利用不同的外源营养通过不同的激活状态成熟时。可溶腺苷酸环化酶（SAC）对于观察到的分子变化至关重要电容，我们将使用独特的工具来调节其活动以测试 SAC调节电容引起的代谢变化的假设。