Crosstalk between metabolic and signaling pathways involved in sperm capacitation

摘要/摘要(不超过30行) 哺乳动物的精子在通过卵巢时获得受精能力。 生殖道中的一种称为获能的过程。在获能过程中，精子 改变他们的活动模式，使他们有能力经历顶体 使卵子反应并使其受精。与获能相关的过程需要能量。 与体细胞相似，精子产生三磷酸腺苷和其他高能化合物 通过大量的协调行动利用环境中的营养物质 代谢途径，包括糖酵解和线粒体氧化 磷酸化。在精子中，这些途径是如何发挥作用的还不清楚。 协调调节以产生足够的能量以供运动和获能。 在这一应用中，我们建议将现代代谢物图谱与 代谢流量分析对精子生理学的贡献 精子使用的不同代谢途径。这些研究将测试 中心假说是精子主动上调其代谢。 获能以产生足够的能量以供运动和其他获能- 受精所必需的相关过程。可溶性腺酰环化酶(SAC) 对于在获能过程中观察到的分子变化是必不可少的。在其他 在上下文中，SAC是一个代谢感应器。因此，我们还将检验这一假设 SAC在精子中充当代谢感受器，调节新陈代谢 获能引起的变化，并调节能量的产生 持续的精子运动能力。 好了！

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. !