TLR signalling affects sperm mitochondrial function and motility via phosphatidylinositol 3-kinase and glycogen synthase kinase-3α
TLR signalling affects sperm mitochondrial function and motility via phosphatidylinositol 3-kinase and glycogen synthase kinase-3α
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TLR 信号通过磷脂酰肌醇 3-激酶和糖原合酶激酶-3α 影响精子线粒体功能和运动性
DOI：
10.1016/j.cellsig.2015.12.002
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发表时间：
2016-03-01
影响因子：
4.8
通讯作者：
Zhou, Hong
中科院分区：
文献类型：
--
作者：
Zhu, Xingxing;Shi, Dongyan;Zhou, Hong
男性和女性生殖道感染可导致不育。这一过程的基本机制尚不清楚。Toll样受体（TLR）识别保守结构，并通过启动激活炎症基因转录的信号对病原体做出反应。在这里，我们证明了精子中的TLR激活通过髓样分化因子88（MyD 88）、磷脂酰肌醇3-激酶（PI 3 K）和糖原合成酶激酶（GSK）-3 α的信号传导降低精子活力。TLR激活后，在线粒体中检测到PI 3 K和GSK 3 α的磷酸化形式，精子中线粒体膜电位受损。此外，TLR激动剂刺激后线粒体ATP水平降低。此外，阻断PI 3 K或GSK 3 α激活可消除这些作用，并逆转TLR诱导的精子活力降低。这些结果确定了一个以前未被认识的TLR信号通路，导致精子线粒体功能障碍，从而降低精子活力。我们的研究揭示了病原体感染影响精子活力并可能导致不育的新机制。(C)由Elsevier Inc.出版。
Infection in male and female genital tracts can lead to infertility. The underlying mechanisms of this process remain unclear. Toll-like receptors (TLRs) recognize conserved structures and respond to pathogens by initiating signals that activate inflammatory gene transcription. Here, we demonstrate that TLR activation in sperm reduces sperm motility via signalling through myeloid differentiation factor 88 (MyD88), phosphatidylinositol 3-kinase (PI3K), and glycogen synthase kinase (GSK)-3 alpha. Upon TLR activation, phosphorylated forms of PI3K and GSK3 alpha were detected in the mitochondria, and the mitochondrial membrane potential was impaired in sperm. In addition, mitochondrial ATP levels were decreased after TLR agonist stimulation. Furthermore, blocking PI3K or GSK3 alpha, activation abrogated these effects and reversed the TLR-induced reduction in sperm motility. These results identify a previously unrecognized TLR signalling pathway that leads to dysfunctional sperm mitochondria, which reduce sperm motility. Our study reveals a novel mechanism by which pathogenic infection affects sperm motility and possibly leads to infertility. (C) 2015 Published by Elsevier Inc.