Folic Acid Alleviates Hydrogen Peroxide-Induced Oxidative Stress in Bovine Placental Trophoblast Cells by Regulating the NRF2/mTOR Signaling Pathway

As one of the important components of placental structure, the integrity of placental trophoblast cells is crucial for placental function. When oxidative stress continues to act on placental trophoblast cells, it can cause changes in placental structure and function. Research has shown that folic acid (FA) has a certain alleviating effect on the functional damage of trophoblast cells caused by oxidative stress, but the mechanism of action is still unclear. Therefore, this study focuses on bovine placental trophoblast cells (BPTCs) to explore the effects and mechanisms by which FA regulates oxidative stress in cells, with the aim of providing a theoretical foundation for improving the reproductive performance of cows. The results show that, compared with the H₂O₂ group, the FA+ H₂O₂ group showed an increase in the cell proliferation index (PI), superoxide dismutase 2 (<i>SOD2</i>), glutathione peroxidase (<i>GSH-px</i>), and catalase (<i>CAT</i>) mRNA expression and total antioxidant capacity (T-AOC) of cells, while the content of reactive oxygen species (ROS) decreased. In addition, the mRNA expression of tight junction factors, nutrient transporters, placental functional factors, mammalian rapamycin (mTOR) and its downstream factors, and nuclear factor erythroid 2-related factor 2 (NRF2) and its downstream factors in the FA+ H₂O₂ group increased, while the protein abundance of nuclear NRF2 decreased. After treatment with the inhibitor ML385, it was found that the protective effect of FA on H₂O₂-induced cellular oxidative damage was alleviated. These results indicate that FA can regulate the NRF2/mTOR signaling pathway, promote the expression of antioxidant factors, and alleviate the damage to the cell barrier and nutrient transport function in BPTCs caused by oxidative stress.