Understanding the Toxin Effects of β-Zearalenol and HT-2 on Bovine Granulosa Cells Using iTRAQ-Based Proteomics

Zearalenone (ZEA) and T-2 are the most common mycotoxins in grains and can enter the animal and human food-chain and cause many health disorders. To elucidate the toxic response profile, we stimulated bovine granulosa cells (GCs) with β-zearalenol or HT-2. Using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic, 178 and 291 differentially expressed proteins (DEPs, fold change ≥ 1.3 and p-value < 0.05) in β-zearalenol and HT-2 groups were identified, respectively. Among these DEPs, there were 66 common DEPs between β-zearalenol and HT-2 groups. These 66 DEPs were associated with 23 biological processes terms, 14 molecular functions terms, and 19 cellular components terms. Most heat shock proteins (HSPs) were involved in the toxic response. Reactive oxygen species accumulation, the endoplasmic reticulum (ER)-stress related marker molecule (GRP78), and apoptosis were activated. β-zearalenol and HT-2 inhibited oestradiol (E₂) production. These results emphasized the important function of HSPs, clarified oxidative stress, and demonstrated the caspase-3 signaling cascade involved in mycotoxin-treated toxic response, along with decreased E₂ production. This study offers new insights into the toxicity of β-zearalenol and HT-2 on ovarian granulosa cells.