Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Tissue Cell. 2020 Oct;66:101381. doi: 10.1016/j.tice.2020.101381. Epub 2020 May 13.
Male infertility is a global problem in modern society of which capacitating defects are a major cause. Previous studies have demonstrated that Ca ionophore A23187 can make mouse sperm capable of fertilizing in vitro, which may aid in clinical treatment of capacitating defects. However, the detailed role and mechanism of Ca in the capacitating process are still unclear especially how A23187 quickly renders sperm immotile and inhibits cAMP/PKA-mediated phosphorylation. We report that A23187 induces a Ca flux in the mitochondria enriched sperm tail and excess Ca inhibits key metabolic enzymes involved in acetyl-CoA biosynthesis, TCA cycle and electron transport chain pathways resulting in reduced ATP and overall energy production, however this flux does not destroy the structure of the sperm tail. Due to the decrease in ATP production, which is the main phosphate group donator and the power of sperm, the sperm is rendered immobile and PKA-mediated phosphorylation is inhibited. Our study proposed a possible mechanism through which A23187 reduces sperm motility and PKA-mediated phosphorylation from ATP generation, thus providing basic data for exploring the functional roles of Ca in sperm in the future.
男性不育是现代社会的一个全球性问题，其中精子获能缺陷是主要原因之一。先前的研究表明钙离子载体 A23187 可以使精子在体外受精，这可能有助于临床治疗精子获能缺陷。然而，钙离子在获能过程中的详细作用和机制仍不清楚，特别是 A23187 如何快速使精子失去活力并抑制 cAMP/PKA 介导的磷酸化。我们报告 A23187 在富含线粒体的精子尾部诱导钙离子流，过量的钙离子抑制参与乙酰辅酶 A 生物合成、三羧酸循环和电子传递链途径的关键代谢酶，导致 ATP 和整体能量产生减少，但这种钙流不会破坏精子尾部的结构。由于 ATP 生成减少，而 ATP 是主要的磷酸基团供体和精子的动力来源，精子失去活力，PKA 介导的磷酸化受到抑制。我们的研究提出了一种可能的机制，即 A23187 通过从 ATP 生成中降低精子活力和 PKA 介导的磷酸化，从而为未来探索钙离子在精子中的功能作用提供了基础数据。
