Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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TLR-1, TLR-2, and TLR-6 MYD88-dependent signaling pathway: A potential factor in the interaction of high-DNA fragmentation human sperm with fallopian tube epithelial cells

  • Zahra Zandieh (Reproductive Sciences and Technology Research Center, Department of Anatomy, Iran University of Medical Sciences) ;
  • Azam Govahi (Endometriosis Research Center, Iran University of Medical Sciences) ;
  • Azin Aghamajidi (Department of Immunology, School of Medicine, Iran University of Medical Sciences) ;
  • Ehsan Raoufi (Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences) ;
  • Fatemehsadat Amjadi (Department of Anatomy, School of Medicine, Iran University of Medical Sciences) ;
  • Samaneh Aghajanpour (Department of Anatomy, School of Medicine, Iran University of Medical Sciences) ;
  • Masoomeh Golestan (Department of Advanced Medical Sciences & Technologies, School of Medicine, Jahrom University of Medical Sciences) ;
  • Reza Aflatoonian (Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine)
  • Received : 2022.08.15
  • Accepted : 2022.12.06
  • Published : 2023.03.31
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Abstract

Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.

Keywords

Acknowledgement

The authors would like to thank the Royan Institute for Reproductive Biomedicine, Tehran, Iran for their cooperation throughout the period of the study.

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