Association and Toxic Mechanism Between Foodborne OTA Exposure and Embryonic Development

This study aimed to integrate bioinformatics and in vivo experiments to explore the embryonic developmental toxicity and specific mechanism of foodborne ochratoxin A (OTA), and to provide new discoveries and evidence for the prevention and control of foodborne contaminants. Bioinformatic analyses were performed to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes (DEGs) and oxidative stress-related DEGs (OSDEGs), and to screen hub genes through protein-protein interaction (PPI) networks; subsequently, ROC curve validation and molecular docking were carried out for the hub genes, followed by construction of a targeted miRNA network. On the other hand, different OTA exposure dose models in pregnant C57BL/6 mice were established to evaluate embryonic development, detect placental oxidative stress indicators, and measure protein expression levels of the PI3K/Akt/Nrf2/HO-1 pathway. The results demonstrated that OSDEGs were mainly enriched in PI3K/Akt pathways. The hub genes exhibited AUC values above 0.75 and molecular docking binding energies ≤ -5 kcal/mol. Additionally, six miRNAs targeting hub genes were predicted. In the established OTA exposure models, high-dose dams showed impaired weight gain, significantly reduced live fetus rates, and fetal malformations compared with controls. In exposure groups, placental glutathione levels decreased while malondialdehyde increased, accompanied by downregulated expression of Nrf2/HO-1 and p-PI3K/p-Akt. In conclusion, OTA can suppress the phosphorylation level of PI3K/Akt, thereby affecting the protein expression of the Nrf2/HO-1 signaling pathway, leading to inhibition of the body's antioxidant capacity and subsequently triggering oxidative stress, causing embryonic developmental toxicity.