Mitochondrial membrane potential disruption pattern in human sperm
Mitochondrial membrane potential disruption pattern in human sperm
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DOI：
10.1093/humrep/dep120
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发表时间：
2009-09-01
影响因子：
6.1
通讯作者：
Villegas, Juana V.
中科院分区：
文献类型：
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作者：
Espinoza, Jaime A.;Paasch, Uwe;Villegas, Juana V.
精子线粒体膜电位（δ Psi(m)）的丧失与精液中活性氧含量高、精子图参数异常和体外受精成功率低有关。在体细胞中，δ Psi(m)的丧失主要与细胞死亡的几种机制有关，主要是半胱天蛋白酶的激活。线粒体功能障碍对精子功能的影响仍未完全阐明，尽管在人类射精中对δ Psi(m)的破坏和半胱天冬酶的激活进行了深入研究。精子中δ Psi(m)的破坏可由抗肿瘤剂白桦酸（BA）外部触发。在这项研究中，我们确定了caspase激活对于ba诱导的人类精子中δ Psi(m)的破坏是否必要。通过游动过程选择有活力且运动能力强的精子细胞，用90 μ g/ml BA孵育。为了阐明ba触发的δ Psi(m)破坏对caspase的依赖性，我们使用了泛caspase抑制剂zVAD-fmk和caspase-3/7抑制剂DEVD-cho。将高运动精子暴露于BA会导致δ Psi(m)的特定破坏（与对照组相比P < 0.001）和相应的caspase-3/7活性增加（与对照组相比P < 0.001）。与zVAD-fmk或DEVD-cho共孵育的精子仅部分抑制ba诱导的δ Psi(m)损失（与对照组相比P < 0.05）。我们发现半胱天冬酶直接参与了BA在人精子细胞中引起的δ Psi(m)的损失。然而，caspase非依赖性通路也可能存在。
Loss of mitochondrial membrane potential (delta Psi(m)) in spermatozoa is correlated with high levels of reactive oxygen species in semen, abnormal spermiogram parameters, and low success rates of IVF. In somatic cells, the loss of delta Psi(m) is primarily associated with several mechanisms of cell death, mainly the activation of caspases. The impact of mitochondrial dysfunction on sperm function is still not fully elucidated, although disruption of delta Psi(m) and activation of caspases are processes thoroughly studied in human ejaculates. Disruption of delta Psi(m) in sperm can be externally triggered by the antineoplastic agent betulinic acid (BA). In this study, we determined whether caspase activation is necessary for the BA-induced disruption of delta Psi(m) in human sperm.Viable and highly motile sperm cells were selected through a swim-up process and incubated with 90 mu g/ml BA. To elucidate the caspase dependency of BA-triggered disruption of delta Psi(m), we used the pan-caspase inhibitor zVAD-fmk and the caspase-3/7 inhibitor DEVD-cho.Exposing highly motile sperm to BA caused a specific disruption of delta Psi(m) (P < 0.001 versus control) and a corresponding increase in caspase-3/7 activity (P < 0.001 versus control). Pre-incubation of the sperm with zVAD-fmk or DEVD-cho only partially inhibited BA-induced loss of delta Psi(m) (P < 0.05 versus control).We found that caspases directly participate in the loss of delta Psi(m) caused by BA in human sperm cells. However, caspase-independent pathways may also be present.