Bta-Let-7d Modulation of Oxidative Stress Induced by Potassium Permanganate 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 the 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 the 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 an upregulation of pro-apoptotic markers, alongside diminished antioxidant capacity. Mechanistically, bta-let-7d targets IGF1R, leading to the 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 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.