Beauvericin Exposure Induces Cell Cycle Arrest and Is Accompanied by Alterations in ERK1/2 and JAK2/STAT3 Signaling in Bovine Mammary Epithelial Cells

Beauvericin (BEA) is an emerging mycotoxin widely detected in feeds in recent years, posing a serious threat to the physiological health of dairy cows. Current studies on the biological toxicity of BEA mainly focus on the reproductive system, while research regarding mammary gland development in dairy cows remains scarce. Therefore, we used bovine mammary alveolar cells (MAC–T) as the research object to investigate the toxic effects of BEA and its underlying mechanisms. Our results demonstrated that BEA induced cell cycle arrest; with increasing doses, BEA altered cell morphology, stretched cell membranes toward both poles and triggered cell death. Further studies revealed that BEA exposure not only promoted intracellular reactive oxygen species (ROS) accumulation but also induced endoplasmic reticulum stress. BEA also suppressed the expression of genes associated with milk fat synthesis, including FASN, ACSS2, FABP3, SCD, DHCR7 and INSIG1. In addition, altered phosphorylation of JAK2/STAT3 and ERK1/2 was also observed following BEA exposure. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that differentially expressed genes (DEGs) were significantly enriched in processes such as cell cycle, cytoskeleton organization and metabolism, which helped to characterize the toxic effects of BEA in bovine mammary epithelial cells.