Endoplasmic reticulum stress is involved in mycotoxin zearalenone induced inflammatory response, proliferation, and apoptosis in goat endometrial stromal cells

Reprod Biol. 2024 Dec;24(4):100948. doi: 10.1016/j.repbio.2024.100948. Epub 2024 Sep 3.

Abstract

Zearalenone (ZEA) is an estrogen-like mycotoxin and is considered a secondary metabolite produced by Fusarium fungi, which are widely found in the surrounding environment. ZEA has been found to cause reproductive dysfunction in female and male animals, but the underlying mechanism remains unclear. Therefore, this study examined cell proliferation, cell apoptosis, autophagy protein expression, and some inflammatory cytokines such as IL-1β and IL-8 of goat endometrial stromal cells (ESCs) induced by different concentrations (0, 15, 30, 60, and 90 µM) of ZEA. The apoptosis rate was detected by flow cytometry. Western Blot and ELISA assay were used to identify the ER stress signaling pathway and some inflammatory cytokines. Our results revealed that ZEA induced cell proliferation and inhibited cell apoptosis at low and middle concentrations, while at high concentrations of ZEA, cell apoptosis was induced in ESCs. Additionally, ZEA induced the ER stress protein markers such as ATF6, IRE1α, EIF2α, and ATF4. LC3 as a marker of autophagy was up-regulated at all concentrations of ZEA. Moreover, IL-1β and IL-8 showed down-regulation at a low concentration of ZEA, but middle and high concentrations showed up-regulation. In the present study, Knockdown ERN1 can inhibit autophagy and the main markers of ER stress. These results suggest that the IRE1 pathway can reduce apoptosis protein markers, down activate IRE1, and unfolded protein response branches such as ATF6 and LC3 in ESCs. Additionally, IL-1β and IL-8 achieve up-regulation under knockdown IRE1, which can block ER stress markers.

Keywords: Autophagy; ER stress; Goat endometrial stromal cells; Mycotoxin; Zearalenone.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Autophagy / drug effects
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Endometrium* / drug effects
  • Endometrium* / metabolism
  • Endoplasmic Reticulum Stress* / drug effects
  • Female
  • Goats*
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Stromal Cells* / drug effects
  • Stromal Cells* / metabolism
  • Zearalenone* / toxicity

Substances

  • Zearalenone