Magnolol enhances yak oocyte maturation and blastocyst quality by improving lipid metabolism and redox homeostasis through a PPARγ-dependent mechanism

Abstract

Abstract Background Reproductive efficiency in yaks is limited by the poor developmental competence of their oocytes during in vitro maturation (IVM). Magnolol (MAG), a natural polyphenolic compound with potent antioxidant activity, has been reported to regulate cellular metabolism and oxidative stress; however, its role in oocyte maturation and early embryonic development remains unclear. Therefore, this study investigated the effects and molecular mechanisms of MAG on yak oocyte maturation and developmental competence. Methods Yak cumulus–oocyte complexes were cultured in IVM medium supplemented with different concentrations of MAG (0, 0.5, 1, 5, and 10 μmol/L). Oocyte maturation, cumulus expansion, oxidative stress indicators, mitochondrial function, apoptosis, and lipid metabolism were evaluated using fluorescence staining, qPCR, and immunofluorescence analysis. Network pharmacology and molecular docking were used to predict potential targets of MAG, and the peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662 was applied to verify the regulatory mechanism occurring during IVM and subsequent embryo development. Results Based on the concentration-screening results, 1 μmol/L MAG was selected for subsequent mechanistic and embryo-development analyses. MAG supplementation significantly improved oocyte maturation and cumulus expansion, enhanced glutathione levels and mitochondrial membrane potential, and reduced reactive oxygen species accumulation and apoptosis. MAG also promoted lipid droplet accumulation and upregulated the expression of lipid metabolism–related genes, including PPARG , CD36 , FABP3 , and FABP4 . Network pharmacology identified PPARγ as a key target of MAG. Pharmacological inhibition of PPARγ with GW9662 markedly reversed MAG-induced improvements in lipid metabolism, antioxidant capacity, and oocyte developmental competence. Furthermore, MAG increased blastocyst formation rate, total cell number, and CDX2 expression while reducing the blastocyst apoptosis. Conclusion MAG improves yak oocyte quality and embryonic developmental competence by promoting lipid homeostasis, maintaining redox balance, and enhancing mitochondrial function. The beneficial effects of MAG are closely associated with the involvement of PPARγ signaling in the regulation of lipid homeostasis. These findings provide a potential strategy for improving the efficiency of yak assisted reproductive technologies.