Abstract: Zearalenone (ZEN) is a fungal toxin with cytotoxic and estrogenic activity which is produced by Fusarium, ZEN has serious toxic impacts on the reproductive system, urinary system and digestive system. At present, the potential mechanism of ZEN on apoptosis of goat endometrial stromal cells (ESCs) remains unclear. In this study, we studied the effect of ZEN on the proliferation and apoptosis of goat ESCs by CCK-8 and flow cytometry in vitro. To investigate whether ZEN affected the proliferation and apoptosis of goat ESCs through endoplasmic reticulum stress (ERS), Real-time PCR and Western blot were used to detect the gene expression levels of ERS and apoptosis. The results showed that ZEN inhibited the proliferation of goat ESCs in a dose-dependent manner. With the increase of ZEN dose, the apoptosis rate of goat ESCs increased significantly. ZEN dose-dependent up-regulation of Caspase-8, Caspase-9 and Bax/Bcl-2 mRNA expression levels. ZEN could significantly up-regulate the expression levels of GRP78 and CHOP mRNA and protein. Meanwhile, the expression levels of ATF6, PERK and IRE1 mRNA were drastically increased. In contrast, the IRE1 pathway could be significantly affected by ZEN. Addition of ERS specific inhibitor 4-PBA or IRE1 specific inhibitor Irestatin 9389 significantly reduced the inhibitory effect of ZEN on ESCs proliferation. These results indicated that ZEN could regulate the apoptotic process of ESCs in goats through the ERS pathway.

Key words: zearalenone, endometrial stromal cells, apoptosis, endoplasmic reticulum stress, goat