Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways.
Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways.
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小鼠精子能量限制和恢复（SER）揭示了新型的代谢途径。
DOI：
10.3389/fcell.2023.1234221
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
哺乳动物的精子必须经过获能才能具有受精能力。在对小鼠的研究中，我们最近开发了一种体外治疗精子的新方法，这种方法可以提高体外受精后的受精率和胚胎发育率。在缺乏营养的培养基中孵育的精子虽然仍能存活，但会失去活力。在重新添加能量底物后，精子恢复活力并具有改进的功能。在这里，我们探讨精子能量限制和恢复（SER）治疗如何影响精子代谢和获能相关的信号。通过细胞外通量分析、代谢物谱分析以及核磁共振（NMR）和质谱（MS）的追踪，我们发现许多代谢物的水平在SER的饥饿阶段发生了变化。特别有趣的是，两种代谢物，AMP和左旋肉碱，在能量受限的精子中显著增加。在重新添加葡萄糖并开始获能后，大多数代谢物水平恢复并接近于未经历饥饿的获能精子中观察到的水平。在对照和ser处理的精子中，在能化条件下孵育上调糖酵解和氧化磷酸化。然而，ATP水平降低，可能反映了电容化过程中能量消耗的增加。13C葡萄糖的通量数据表明，与其他具有高葡萄糖消耗率的细胞类似，丙酮酸转化为13C-乳酸，并以较低的效率转化为13C-醋酸盐，然后释放到培养液中。此外，我们的代谢通量数据显示，外源供应的葡萄糖转化为柠檬酸盐，这提供了精子细胞和体细胞一样，糖酵解产物可以转化为克雷布斯循环代谢物的证据。
Mammalian sperm must undergo capacitation to become fertilization-competent. While working on mice, we recently developed a new methodology for treating sperm in vitro, which results in higher rates of fertilization and embryo development after in vitro fertilization. Sperm incubated in media devoid of nutrients lose motility, although they remain viable. Upon re-adding energy substrates, sperm resume motility and become capacitated with improved functionality. Here, we explore how sperm energy restriction and recovery (SER) treatment affects sperm metabolism and capacitation-associated signaling. Using extracellular flux analysis and metabolite profiling and tracing via nuclear magnetic resonance (NMR) and mass spectrometry (MS), we found that the levels of many metabolites were altered during the starvation phase of SER. Of particular interest, two metabolites, AMP and L-carnitine, were significantly increased in energy-restricted sperm. Upon re-addition of glucose and initiation of capacitation, most metabolite levels recovered and closely mimic the levels observed in capacitating sperm that have not undergone starvation. In both control and SER-treated sperm, incubation under capacitating conditions upregulated glycolysis and oxidative phosphorylation. However, ATP levels were diminished, presumably reflecting the increased energy consumption during capacitation. Flux data following the fate of 13C glucose indicate that, similar to other cells with high glucose consumption rates, pyruvate is converted into 13C-lactate and, with lower efficiency, into 13C-acetate, which are then released into the incubation media. Furthermore, our metabolic flux data show that exogenously supplied glucose is converted into citrate, providing evidence that in sperm cells, as in somatic cells, glycolytic products can be converted into Krebs cycle metabolites.
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影响因子：
4.5
作者：
Gervasi MG;Visconti PE
通讯作者：
Visconti PE
影响因子：
64.5
作者：
Chung JJ;Shim SH;Everley RA;Gygi SP;Zhuang X;Clapham DE
通讯作者：
Clapham DE
影响因子：
5.6
作者：
Martin-Hidalgo D;Hurtado de Llera A;Calle-Guisado V;Gonzalez-Fernandez L;Garcia-Marin L;Bragado MJ
通讯作者：
Bragado MJ
影响因子：
--
作者：
Vadnais ML;Lin AM;Gerton GL
通讯作者：
Gerton GL
影响因子：
2.8
作者：
Dahan, Tsipora;Breitbart, Haim
通讯作者：
Breitbart, Haim