1. Academic Validation
  2. 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

  • Cell Signal. 2016 Mar;28(3):148-156. doi: 10.1016/j.cellsig.2015.12.002.
Xingxing Zhu 1 Dongyan Shi 2 Xiaoqian Li 2 Weijuan Gong 3 Fengjiao Wu 2 Xuejiang Guo 1 Hui Xiao 4 Lixin Liu 5 Hong Zhou 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
  • 2 Department of Immunology, Nanjing Medical University, Nanjing 210029, China.
  • 3 Department of Microbiology & Immunology, Yangzhou University, Yangzhou 225009, China.
  • 4 Institute of Pasteur Shanghai, Chinese Academy of Sciences, Shanghai 200025, China.
  • 5 Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada.
  • 6 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China. Electronic address: hzhou@njmu.edu.cn.
Abstract

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)-3α. Upon TLR activation, phosphorylated forms of PI3K and GSK3α 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 GSK3α 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.

Keywords

GSK3α; Mitochondrial function; PI3K; Sperm motility; TLR signalling.

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