Role of MFN2 in bovine embryonic development and the mitigation of ER stress.

Abstract

This study investigated the role of mitochondrial fusion protein-2 (MFN2) in bovine embryonic development and its relationship with endoplasmic reticulum (ER) stress, aiming to increase the efficiency of in vitro embryo culture. Western blot analysis revealed that MFN2 expression peaked at the 2-cell stage, decreased at the 4-cell stage, and gradually increased from the 6-8-cell stage to the blastocyst stage. Inhibiting MFN2 at the zygote stage reduced blastocyst formation and proliferation, and this damage was partially reversed by the ER stress protective agent TUDCA. MFN2 inhibition also led to the decreased formation of the inner cell mass (ICM) and reduced expression of the totipotent genes CDX2 and SOX2. Additionally, reactive oxygen species (ROS) levels increased following MFN2 inhibition but decreased after TUDCA treatment. The expression of antioxidative stress-related genes (SOD and CAT) was downregulated after MFN2 inhibition but upregulated following TUDCA treatment. Furthermore, MFN2 inhibition reduced ER fluorescence intensity and increased the expression of UPR signaling markers (GRP78, XBP1, CHOP, IRE1, and ATF6), indicating increased ER stress. TUDCA administration reversed these effects, restoring MFN2 levels and reducing apoptosis. In conclusion, MFN2 is essential for bovine embryonic development because it regulates ER stress and maintains cell function, with MFN2 deficiency leading to developmental disorders and cell damage. ER stress protectors such as TUDCA can effectively mitigate these negative effects, highlighting a potential strategy for improving in vitro embryo culture efficiency.