Obesity is increasingly recognized as a major factor contributing to female reproductive dysfunction and declining fertility. Excessive lipid accumulation and oxidative stress under obese conditions can disrupt mitochondrial homeostasis in oocytes, leading to impaired meiotic maturation, abnormal cytoskeletal organization, DNA damage, and reduced embryonic developmental competence. However, effective interventions targeting obesity-associated oocyte deterioration remain limited.

BAM15 is a novel mitochondrial uncoupler with improved mitochondrial selectivity and lower cytotoxicity than conventional uncouplers. Although BAM15 has shown beneficial effects on metabolic regulation and oxidative stress, its role in obesity-induced reproductive impairment has not been fully understood.

Recently, the research group led by Shaochen Sun at Nanjing Agricultural University published a study entitled “BAM15 improves oocyte quality against obesity via PPARγ-dependent mitochondrial function” in Protein & Cell. Combining single-cell transcriptomic analysis, molecular docking, and pharmacological approaches, the study systematically revealed the mechanisms by which BAM15 improves oocyte quality in obese mice fed a high-fat diet.

The study demonstrated that BAM15 markedly rescued obesity-induced defects in oocyte maturation and embryonic development. Transcriptomic analyses showed that BAM15 restored the expression of genes associated with cytoskeletal organization, mitochondrial function, and energy metabolism. Further experiments revealed that BAM15 corrected spindle abnormalities, improved microtubule acetylation, reduced excessive actin accumulation, and alleviated ROS accumulation and DNA damage in oocytes from obese mice. Importantly, BAM15 restored mitochondrial membrane potential and mitochondrial dynamics by regulating p-DRP1- and Parkin-mediated pathways. Mechanistically, the protective effects of BAM15 were largely dependent on activation of the PPARγ signaling pathway, highlighting PPARγ-mediated mitochondrial homeostasis as a critical mechanism underlying improved oocyte quality in obesity.
https://doi.org/10.1093/procel/pwag035