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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Glyceraldehyde 3-phosphate dehydrogenase-S a sperm-specific glycolytic enzyme is required for sperm motility and male fertility
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Glyceraldehyde 3-phosphate dehydrogenase-S a sperm-specific glycolytic enzyme is required for sperm motility and male fertility

机译：精子运动性和雄性育性需要甘油醛3-磷酸脱氢酶-S一种精子特有的糖酵解酶

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摘要

Although glycolysis is highly conserved, it is remarkable that several unique isozymes in this central metabolic pathway are found in mammalian sperm. Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS) is the product of a mouse gene expressed only during spermatogenesis and, like its human ortholog (GAPD2), is the sole GAPDH isozyme in sperm. It is tightly bound to the fibrous sheath, a cytoskeletal structure that extends most of the length of the sperm flagellum. We disrupted Gapds expression by gene targeting to selectively block sperm glycolysis and assess its relative importance for in vivo sperm function. Gapds–/– males were infertile and had profound defects in sperm motility, exhibiting sluggish movement without forward progression. Although mitochondrial oxygen consumption was unchanged, sperm from Gapds–/– mice had ATP levels that were only 10.4% of those in sperm from WT mice. These results imply that most of the energy required for sperm motility is generated by glycolysis rather than oxidative phosphorylation. Furthermore, the critical role of glycolysis in sperm and its dependence on this sperm-specific enzyme suggest that GAPDS is a potential contraceptive target, and that mutations or environmental agents that disrupt its activity could lead to male infertility.
机译：尽管糖酵解是高度保守的，但值得注意的是，在哺乳动物的精子中发现了该中央代谢途径中的几种独特的同工酶。甘油醛3-磷酸脱氢酶S（GAPDS）是仅在精子发生过程中表达的小鼠基因的产物，并且像其人类直系同源物（GAPD2）一样，是精子中唯一的GAPDH同工酶。它与纤维鞘紧密结合，纤维鞘是精子鞭毛大部分长度的细胞骨架结构。我们通过靶向基因来选择性地阻断精子糖酵解，破坏了Gapds的表达，并评估了其对体内精子功能的相对重要性。 Gapds – / – 雄性不育，精子运动能力严重缺陷，运动迟钝，无前移。尽管线粒体耗氧量没有变化，但Gapds – / – 小鼠的精子中的ATP水平仅为野生型小鼠精子中的ATP水平的10.4％。这些结果暗示，精子运动所需的大部分能量是通过糖酵解而不是氧化磷酸化产生的。此外，糖酵解在精子中的关键作用及其对这种精子特异酶的依赖性表明，GAPDS是潜在的避孕靶标，破坏其活性的突变或环境因素可能导致男性不育。

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