Bta-let-7d Modulation of Potassium Permanganate Induced Oxidative Stress in Bovine Endometrial Cells via IGF1R/PI3K/AKT Signaling Pathway

Oxidative stress is a significant factor affecting reproductive efficiency in dairy cows, contributing to conditions such as endometritis that impair fertility and milk production. This study investigates the molecular mechanisms by which bta-let-7d modulates oxidative stress responses induced by potassium permanganate (KMnO₄) in bovine endometrial epithelial cells (BEECs). Using KMnO₄ to induce oxidative stress, we observed significant increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, accompanied by decreased activities of antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD). Quantitative PCR and Western blot analyses indicated a negative correlation between IGF1R and bta-let-7d expression in oxidative stress-affected tissues, suggesting opposing roles in managing stress responses. Following KMnO₄ treatment, there was marked downregulation of anti-apoptotic genes and upregulation of pro-apoptotic markers, alongside diminished antioxidant capacity. Mechanistically, bta-let-7d targets IGF1R, leading to suppression of the PI3K/AKT signaling pathway and exacerbating oxidative damage. In vivo experiments further confirmed the impact of KMnO₄ exposure on IGF1R expression. These findings provide novel insights into the mechanisms by which KMnO₄ induces oxidative stress and apoptosis in the bovine uterus. They highlight the potential for therapeutic strategies targeting the bta-let-7d/IGF1R axis to enhance reproductive health management in dairy cows, offering a promising avenue for mitigating oxidative stress-related reproductive disorders.