Heat Stress Reduces Sperm Motility via Activation of Glycogen Synthase Kinase-3α and Inhibition of Mitochondrial Protein Import.
Heat Stress Reduces Sperm Motility via Activation of Glycogen Synthase Kinase-3α and Inhibition of Mitochondrial Protein Import.
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热应激通过激活糖原合酶激酶 3 α 和抑制线粒体蛋白输入来降低精子活力
DOI：
10.3389/fphys.2017.00718
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发表时间：
2017
影响因子：
4
通讯作者：
He B
中科院分区：
文献类型：
--
作者：
Gong Y;Guo H;Zhang Z;Zhou H;Zhao R;He B
高温暴露对动物生殖功能的不良影响一直受到人们的关注。然而，热应激（HS）诱导的精子活力下降的分子基础尚未完全阐明。我们推测HS的恶化作用可能是通过线粒体功能和ATP合成的损伤来介导的。为了验证这一假设，我们使用成熟的猪精子作为模型，探讨HS对线粒体功能和精子活力的影响。暴露于42 ° C（HS）6 h可导致精子前向运动力显著降低。同时，HS诱导线粒体功能障碍，表现为膜电位、呼吸链复合物I和IV活性以及三磷酸腺苷（ATP）含量的降低。外源性ATP可阻断这种作用，提示ATP合成减少是HS诱导精子活力降低的关键步骤。在分子水平上，HS精子线粒体蛋白质含量显著降低。值得注意的是，细胞色素c氧化酶亚基4，这是在细胞质中合成和易位到线粒体，是显着降低HS精子线粒体。糖原合成酶激酶-3 α（GSK3 α）是精子运动的负性调节因子，在HS后被Ser21磷酸化失活。GSK3 α抑制剂CHIR 99021能消除HS对精子及其线粒体的影响。综上所述，我们的研究结果表明，HS通过下调线粒体活性和ATP合成量来影响精子活力，这涉及GSK3 α的去磷酸化和线粒体重塑的干扰。
The adverse effects of high environmental temperature exposure on animal reproductive functions have been concerned for many decades. However, the molecular basis of heat stress (HS)-induced decrease of sperm motility has not been entirely elucidated. We hypothesized that the deteriorate effects of HS may be mediated by damage of mitochondrial function and ATP synthesis. To test this hypothesis, we use mature boar sperm as model to explore the impacts of HS on mitochondrial function and sperm motility. A 6 h exposure to 42°C (HS) induced significant decrease in sperm progressive motility. Concurrently, HS induced mitochondrial dysfunction that is indicated by decreased of membrane potential, respiratory chain complex I and IV activities and adenosine triphosphate (ATP) contents. Exogenous ATP abolished this effect suggesting that reduced of ATP synthesis is the committed step in HS-induced reduction of sperm motility. At the molecular level, the mitochondrial protein contents were significantly decreased in HS sperm. Notably, the cytochrome c oxidase subunit 4, which was synthesized in cytoplasm and translocated into mitochondria, was significantly lower in mitochondria of HS sperm. Glycogen synthase kinase-3α (GSK3α), a negative regulator of sperm motility that is inactivated by Ser21 phosphorylation, was dephosphorylated after HS. The GSK3α inhibitor CHIR99021 was able to abolish the effects of HS on sperm and their mitochondria. Taken together, our results demonstrate that HS affects sperm motility through downregulation of mitochondrial activity and ATP synthesis yield, which involves dephosphorylation of GSK3α and interference of mitochondrial remodeling.
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影响因子：
3.7
作者：
Lee, Jamie A.;Spidlen, Josef;Boyce, Keith;Cai, Jennifer;Crosbie, Nicholas;Dalphin, Mark;Furlong, Jeff;Gasparetto, Maura.;Goldberg, Michael;Goralczyk, Elizabeth M.;Hyun, Bill;Jansen, Kirstin;Kollmann, Tobias;Kong, Megan;Leif, Robert;McWeeney, Shannon;Moloshok, Thomas D.;Moore, Wayne;Nolan, Garry;Nolan, John;Nikolich-Zugich, Janko;Parrish, David;Purcell, Barclay;Qian, Yu;Selvaraj, Biruntha;Smith, Clayton;Tchuvatkina, Olga;Wertheimer, Anne;WilkinSon, Peter;Wilson, Christopher;Wood, James;Zigon, Robert;Scheuermann, Richard H.;Brinkman, Ryan R.
通讯作者：
Brinkman, Ryan R.
影响因子：
4.8
作者：
Kaidanovich-Beilin O;Beaulieu JM;Jope RS;Woodgett JR
通讯作者：
Woodgett JR
影响因子：
6.1
作者：
Marchetti, C;Obert, G;Marchetti, P
通讯作者：
Marchetti, P
影响因子：
3.5
作者：
Downs, CA;Heckathorn, SA
通讯作者：
Heckathorn, SA
影响因子：
5.6
作者：
He, Bin;Zhang, Nana;Zhao, Ruqian
通讯作者：
Zhao, Ruqian