Metabolic Substrates Exhibit Differential Effects on Functional Parameters of Mouse Sperm Capacitation
Metabolic Substrates Exhibit Differential Effects on Functional Parameters of Mouse Sperm Capacitation
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DOI：
10.1095/biolreprod.112.102673
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发表时间：
2012-09-01
影响因子：
3.6
通讯作者：
O'Brien, Deborah A.
中科院分区：
文献类型：
--
作者：
Goodson, Summer G.;Qiu, Yunping;O'Brien, Deborah A.
虽然大量的证据表明，精子ATP生产通过糖酵解是必需的哺乳动物精子功能和男性生育力，冲突的报告，涉及多个物种出现了关于个人糖酵解或线粒体底物的能力，以支持在获能过程中发生的生理变化。获能所需的信号通路缺陷的几种小鼠模型表现出精子ATP水平的降低，表明精子代谢和信号转导级联之间的调节相互作用。为了更好地了解这些相互作用，我们进行了定量研究小鼠精子在整个2小时的体外获能期，并比较了在相同条件下测定的单一底物的影响。多种糖酵解和非糖酵解底物维持精子ATP水平和相当的运动百分比，但只有葡萄糖和甘露糖支持超活化。这些单糖和果糖支持酪氨酸磷酸化的完整模式，而非糖酵解底物支持至少部分酪氨酸磷酸化。抑制糖酵解损害运动的存在下，葡萄糖，果糖，或丙酮酸，但不存在的羟基丁酸。另外的解偶联剂氧化磷酸化减少运动与丙酮酸或羟基丁酸作为底物，但出乎意料地刺激超活化与果糖。更详细地研究葡萄糖和果糖之间的差异，我们证明了葡萄糖的活性代谢导致超活化。葡萄糖和果糖之间的差异似乎是下游的细胞内pH值的变化，这上升到相当的水平，在孵育过程中与任何基板。精子氧化还原途径受到不同的影响，与果糖孵育期间产生的相关代谢产物和活性氧比与葡萄糖孵育期间产生的水平更高。
Although substantial evidence exists that sperm ATP production via glycolysis is required for mammalian sperm function and male fertility, conflicting reports involving multiple species have appeared regarding the ability of individual glycolytic or mitochondrial substrates to support the physiological changes that occur during capacitation. Several mouse models with defects in the signaling pathways required for capacitation exhibit reductions in sperm ATP levels, suggesting regulatory interactions between sperm metabolism and signal transduction cascades. To better understand these interactions, we conducted quantitative studies of mouse sperm throughout a 2-h in vitro capacitation period and compared the effects of single substrates assayed under identical conditions. Multiple glycolytic and nonglycolytic substrates maintained sperm ATP levels and comparable percentages of motility, but only glucose and mannose supported hyperactivation. These monosaccharides and fructose supported the full pattern of tyrosine phosphorylation, whereas nonglycolytic substrates supported at least partial tyrosine phosphorylation. Inhibition of glycolysis impaired motility in the presence of glucose, fructose, or pyruvate but not in the presence of hydroxybutyrate. Addition of an uncoupler of oxidative phosphorylation reduced motility with pyruvate or hydroxybutyrate as substrates but unexpectedly stimulated hyperactivation with fructose. Investigating differences between glucose and fructose in more detail, we demonstrated that hyperactivation results from the active metabolism of glucose. Differences between glucose and fructose appeared to be downstream of changes in intracellular pH, which rose to comparable levels during incubation with either substrate. Sperm redox pathways were differentially affected, with higher levels of associated metabolites and reactive oxygen species generated during incubations with fructose than during incubations with glucose.