Hao Sheng

Mammalian oocyte maturation is a metabolically demanding process relying on lipid metabolism that supplies energy, structural substrates, and signaling mediators. However, a comprehensive cross-species understanding of the dynamic requirement for lipids during this process remains elusive, hindering the optimization of assisted reproductive technologies. Utilizing an integrated single-cell transcriptomic and targeted lipidomic approach, we mapped the metabolic landscape of bovine oocyte maturation. Our analysis uncovered a global transcriptional downregulation, with 3259 genes suppressed during the transition from the germinal vesicle (GV) to the metaphase II (MII) stage. This was particularly apparent in lipid catabolism pathways (e.g., for ACAA1), while mitochondrial energy production genes (ATP6) were upregulated. Lipidomics indicated a selective depletion of saturated fatty acids (SFAs; e.g., C16:0, C18:0) in MII oocytes, while monounsaturated (MUFAs) and polyunsaturated fatty acids (PUFAs) were preferentially retained. Integrated network analysis specified hexadecanoic acid (C16:0) as a central metabolic hub, which rewires its interactions from biosynthetic genes (FASN, ELOVL6) in GV oocytes to degradative enzymes (ACADVL, HADH) in MII oocytes. Expanding to a cross-species transcriptomic atlas, we identified a core set of 59 lipid metabolism genes conserved across bovine, mouse, and human oocytes. Despite this conservation, we discovered stark species-specific regulatory strategies: bovine and human oocytes significantly downregulated fatty acid degradation and elongation post-maturation, whereas murine oocytes maintain pathway activity, upregulating key regulators like Acsl3. Our work unveils an evolutionarily conserved core lipid metabolic program in mammalian oocytes that is adaptively tuned to meet species-specific physiological demands. Bovine and human oocytes prioritize catabolic flexibility, using SFAs for energy, while mouse oocytes maintain their anabolic capacity for membrane biosynthesis. These findings provide a transformative resource for the field, offering biomarkers for oocyte quality and a rationale for enhancing species-tailored lipid formulations to develop in vitro maturation systems and amend reproductive outcomes in both agriculture and medicine.

A well-regulated metabolism is crucial for optimal oocyte development and embryonic health. However, the metabolic framework governing oocyte maturation remains poorly understood. Using bovine oocytes as a model, we examined metabolomic and transcriptomic alterations during the transition from the germinal vesicle (GV) to the metaphase II (MII) stage. Our findings reveal distinct metabolic shifts, including suppressed β-oxidation combined with the accumulation of long-chain fatty acids (LCFAs). Notably, progesterone emerged as a key regulator of meiotic resumption through its influence on cAMP levels. We also observed enhanced glycolysis, moderate activation of the citric acid cycle (TCA cycle), and suppression of oxidative phosphorylation (OXPHOS), alongside reduced urea cycle flux and shifts in amino acid metabolism favoring glutamate synthesis. Intriguingly, discrepancies between metabolic and transcriptional activities in pathways such as the TCA cycle and nucleotide metabolism suggest asynchronous regulation. These findings provide a comprehensive multi-omics resource, advancing our understanding of the dynamic metabolic and transcriptional landscape during bovine oocyte maturation.