2. Academic Validation
  3. Oleuropein restores oocyte competence during SIRT1 inhibition via SIRT1/NRF2-mediated redox and metabolic reprogramming in porcine oocytes

Oleuropein restores oocyte competence during SIRT1 inhibition via SIRT1/NRF2-mediated redox and metabolic reprogramming in porcine oocytes

  • Theriogenology. 2026 May:256:117873. doi: 10.1016/j.theriogenology.2026.117873.
Nenghao Cao 1,  Huilin Peng 1,  Juntong Zhang 1,  Yuhao Zhang 1,  Siying Liang 1,  Minghui Zhao 2,  Yongnan Xu 1,  Dongli Li 1,  Yinghua Li 3
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529000, China.
  • 2 Department of Animal Science, Qingdao Agricultural University, No.700 Changcheng Road, 266000, Shandong, China.
  • 3 Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529000, China. Electronic address: [email protected].
PMID: 41698313 DOI: 10.1016/j.theriogenology.2026.117873
Abstract

Inhibition of Sirtuin 1 (SIRT1) impairs porcine oocyte maturation and embryonic development. Herein, we investigated whether oleuropein (OLE) restores oocyte quality compromised by the SIRT1 Inhibitor EX527. Treatment with EX527 (1 μM) significantly suppressed SIRT1 expression and reduced first polar body extrusion (Control: 74.0 ± 2.8% vs. EX527: 59.9 ± 1.1%, p < 0.001), cleavage rate, blastocyst formation (Control: 43.8 ± 5.4% vs. EX527: 30.4 ± 5.9%, p < 0.05), and cell number. EX527 also induced oxidative stress, as evidenced by increased ROS levels and decreased GSH content, mitochondrial dysfunction (reduced mitochondrial abundance, ATP content, and membrane potential), lipid dysregulation (reduced fatty acids and lipid droplets), and increased Apoptosis and Autophagy, as indicated by upregulated CB, Bax, ERK1, LC3β, and p62 expression. Co-treatment with OLE (5 μM) significantly restored first polar body extrusion (EX527: 59.4 ± 2.0% vs. EX527 + OLE: 69.7 ± 1.3%, p < 0.001), cleavage rate, blastocyst formation (EX527: 25.3 ± 2.4% vs. EX527 + OLE: 41.7 ± 6.0%, p < 0.01), and cell number. OLE reactivated the SIRT1/NRF2 pathway, improved redox homeostasis (upregulated CAT, SOD1, and SOD2 expression), enhanced mitochondrial biogenesis (increased TFB1M and NRF1 expression), normalised lipid metabolism (upregulated PPARγ, ACACA, and PLIN2), and attenuated aberrant apoptotic and autophagic signalling. The SIRT1 Activator resveratrol (2 μM) produced comparable effects. Collectively, these results indicate that OLE mitigates the detrimental effects of SIRT1 inhibition via the SIRT1/NRF2 axis and promotes cytoplasmic maturation, suggesting potential applications in assisted reproduction.

Keywords

Mitochondrial function; Oleuropein; Oxidative stress; Porcine oocyte maturation; SIRT1/NRF2 axis.

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