Increased mitochondrial activity upon CatSper channel activation is required for mouse sperm capacitation.
Increased mitochondrial activity upon CatSper channel activation is required for mouse sperm capacitation.
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DOI：
10.1016/j.redox.2021.102176
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发表时间：
2021-11-01
期刊：
影响因子：
11.4
通讯作者：
Sapiro R
中科院分区：
文献类型：
--
作者：
Ferreira JJ;Cassina A;Irigoyen P;Ford M;Pietroroia S;Peramsetty N;Radi R;Santi CM;Sapiro R
为了使卵母细胞受精，精子必须经历几个被称为获能的生化和功能变化。获能中的一个关键事件是通过精子阳离子通道的钙内流(CatSper)。然而，这种钙内流下游获能的分子机制还不完全清楚。获能也与线粒体耗氧量的增加有关，一些证据表明，受调控的钙进入线粒体可以提高氧化呼吸的效率。因此，我们假设在获能过程中通过CatSper的钙内流增加了线粒体的钙浓度和线粒体的效率，从而促进了精子的过度激活和受精能力。为了验证这一假设，我们使用了高分辨率呼吸测量法来测量小鼠精子线粒体的活动。我们还测量了野生型和CatSper基因敲除小鼠精子线粒体膜电位、获能过程中的ATP/ADP交换以及线粒体钙离子浓度。我们发现，在获得能力的野生型精子中，线粒体活性的增加与线粒体钙浓度的增加是平行的。这种效应在CatSper基因敲除小鼠的精子中是钝化的。重要的是，这些机制对于野生型小鼠的最佳超激活和受精是必要的，正如使用线粒体抑制剂所证实的那样。因此，我们描述了一种新的精子获能机制。这项工作有助于我们理解线粒体在精子生理学中的作用，并为生育治疗和男性避孕开辟了新的分子靶点。
To fertilize an oocyte, sperm must undergo several biochemical and functional changes known as capacitation. A key event in capacitation is calcium influx through the cation channel of sperm (CatSper). However, the molecular mechanisms of capacitation downstream of this calcium influx are not completely understood. Capacitation is also associated with an increase in mitochondrial oxygen consumption, and several lines of evidence indicate that regulated calcium entry into mitochondria increases the efficiency of oxidative respiration. Thus, we hypothesized that calcium influx through CatSper during capacitation increases mitochondrial calcium concentration and mitochondrial efficiency and thereby contributes to sperm hyperactivation and fertilization capacity. To test this hypothesis, we used high-resolution respirometry to measure mouse sperm mitochondrial activity. We also measured mitochondrial membrane potential, ATP/ADP exchange during capacitation, and mitochondrial calcium concentration in sperm from wild-type and CatSper knockout mice. We show that the increase in mitochondrial activity in capacitated wild-type sperm parallels the increase in mitochondrial calcium concentration. This effect is blunted in sperm from CatSper knockout mice. Importantly, these mechanisms are needed for optimal hyperactivation and fertilization in wild-type mice, as confirmed by using mitochondrial inhibitors. Thus, we describe a novel mechanism of sperm capacitation. This work contributes to our understanding of the role of mitochondria in sperm physiology and opens the possibility of new molecular targets for fertility treatments and male contraception.
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影响因子：
1.9
作者：
Ho, Katharine;Wolff, Collin A.;Suarez, Susan S.
通讯作者：
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影响因子：
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作者：
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影响因子：
3.6
作者：
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影响因子：
3.9
作者：
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通讯作者：
DENTON, RM
DOI：
10.1530/rep-15-0102
发表时间：
2015-08
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Correia J;Michelangeli F;Publicover S
通讯作者：
Publicover S