Comparative studies on the regulation of metabolism during sperm capacitation

摘要/摘要 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 反应并使卵母细胞受精。这些与获能相关的过程需要 能量，精子依赖于环境中的营养才能完成 他们。精子通过时会接触到周围环境中的不同营养物质。 从附睾尾部储存到输卵管，它们将在那里相遇 并使卵母细胞受精。在上一个资助期，我们证明了 提供外源葡萄糖的精子通过糖酵解和氧化产生ATP 磷酸化，并通过这两个途径增加葡萄糖的利用 使精子获能。此外，我们还发现，获能精子会改变精子的活性 通过磷酸戊糖途径和精子去外源 营养物质可以代谢内源性能量来源。我们现在提议申请 现代代谢物图谱与代谢通量分析相结合，以确定如何 精子协调调节它们的代谢途径，并利用不同的 外源营养物质在成熟时通过不同的激活状态。可溶的 腺酰环化酶(SAC)对观察到的分子变化是必不可少的 我们将使用我们独特的工具来调节它的活动来测试 假设SAC调节获能引起的代谢变化。

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.