Endoplasmic reticulum stress is involved in the T‐2 toxin‐induced apoptosis in goat endometrium epithelial cells

Abstract

T-2 toxin is one of the trichothecene mycotoxins commonly found in animal feed and agricultural products. Ingestion of T-2 toxin by animals results in acute and chronic diseases, as well as reproductive failure. This study aimed at investigating the role of endoplasmic reticulum (ER) stress in T-2 toxin-induced apoptosis in goat endometrium epithelial cells. Flow cytometry and cell viability assay showed that T-2 toxin significantly induced cell apoptosis, which was accompanied with increased expression of cleaved-caspase-3. The altered expression of two ER stress markers CHOP and GRP78 proved that ER stress is involved in the T-2 toxin-induced apoptosis. 4-phenylbutyrate pretreatment was applied to relieve the ER stress, pretreated endometrium epithelial cells showed a decreased apoptosis level and the expression pattern of CHOP and GRP78 was reversed. The key genes involved in signaling pathways of ER stress-associated apoptosis were examined, which showed that the IRE1-JNK and PERK-ATF4-CHOP signal transduction pathways are both activated. Moreover, the level of cytokines including interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor-α decreased in the T-2 toxin-treated cells. While the 4-phenylbutyrate pretreatment elevates the cytokine levels after T-2 treatment. Collectively, these results suggest that ER stress contributes to the T-2 toxin-induced apoptosis and decreased cytokine levels in goat endometrium epithelial cells. This study offers new insight into the molecular mechanisms of T-2 toxicity on reproductive cells.