Spliced X-box binding protein 1 (XBP1s) protects spermatogonial stem cells (SSCs) from lipopolysaccharide (LPS)-induced damage by regulating the testicular microenvironment

Theriogenology. 2022 Oct 1:191:132-140. doi: 10.1016/j.theriogenology.2022.07.014. Epub 2022 Aug 3.

Abstract

XBP1 is a transcription factor that plays a central role in controlling cellular responses to endoplasmic reticulum stress (ERS). Under stress conditions, the transcriptionally active form of XBP1 is generated by splicing of XBP1 mRNA by the ER-resident protein inositol-requiring enzyme-1α (IRE1α). This study aimed to investigate the role of XBP1 in male reproductive disorders. XBP1s-overexpressing goat spermatogonial stem cells (gSSCs) showed higher proliferative ability in vitro and in vivo. These cells also showed higher antioxidant capacity. In comparison, XBP1 knockdown significantly suppressed proliferation. Further analysis showed that XBP1 could stimulate the secretion of IL-6 from macrophages. Overall, the results indicate that XBP1s functions to enhance the proliferation ability and antioxidant capacity of gSSCs, potentially through a mechanism involving the regulation of gSSCs by macrophages.

Keywords: Goat; Proliferation; SSCs; XBP1s.

MeSH terms

  • Adult Germline Stem Cells* / metabolism
  • Animals
  • Antioxidants
  • Endoplasmic Reticulum Stress
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Lipopolysaccharides* / pharmacology
  • Male
  • Protein Serine-Threonine Kinases
  • X-Box Binding Protein 1 / genetics
  • X-Box Binding Protein 1 / metabolism

Substances

  • Antioxidants
  • Lipopolysaccharides
  • X-Box Binding Protein 1
  • Protein Serine-Threonine Kinases
  • Endoribonucleases