Bushen Tiaochong Recipe induces resistance to apoptosis in oocytes by activating the JNK pathway, inhibiting mitochondrial autophagy and promoting mitochondrial fusion

Abstract

Abstract Background: The mechanisms underlying ovarian function regulation and decline have been a hot topic of research. Based on the traditional Chinese medicine concept of "pattern differentiation-physiologic system-pathway analysis," a systematic characterization method can be used to investigate these issues. In this study, we used microproteomics techniques to compare the differential protein expression in oocytes of diminished ovarian reserve (DOR) mice, and drug-treated mice, and to comprehensively analyze the regulatory effects of Bushen Tiaochong Recipe (BSTCR) on the level and functional effects of protein expression in DOR mice. Methods: There were 10 mice in each of the groups, which included the blank group, the model group, the Western medicine group, and the traditional Chinese medicine group. After 6 weeks of gavage, superovulation was induced in the mice, and seven eggs was collected from each mouse for testing. We analyzed and compared the differentially expressed proteins in oocytes of DOR mice and drug-treated mice. Results: Using microproteomic technology, we found that the expression of the apoptosis-related proteins BAX and MK09 was significantly downregulated after treatment with BSTCR, and this may inhibit oocyte apoptosis by affecting the JNK-c-Jun pathway. The core proteins UBP30 and MOB1B were significantly downregulated, inhibiting mitophagy to exert antiapoptotic and cell growth effects, which are potential targets of BSTCR. Conclusion: Overall, we found that BSTCR regulates the expression of MFN1, promotes mitochondrial fusion, and enhances mitochondrial function. Furthermore, BSTCR exerts anti-apoptotic and growth-promoting effects on oocytes by inhibiting mitochondrial autophagy and promoting mitochondrial fusion.