Salidroside May Attenuate Palmitic Acid-Induced Bovine Oocyte Impairment Associated with Mitochondrial and Antioxidant Restoration

Negative energy balance (NEB) in postpartum dairy cows elevates systemic non-esterified fatty acid (NEFA) levels, including palmitic acid (PA), which impair oocyte quality and contribute to reduced reproductive performance. Salidroside (SAL) has attracted attention for its prominent role in maintaining mitochondrial homeostasis. However, whether SAL can alleviate PA-induced oocyte damage remains unclear. Therefore, the present study was designed to investigate the protective effects of SAL against PA-induced oocyte damage and to explore the underlying mechanisms. We found that 0.2 mM PA triggered oxidative stress in oocytes, as evidenced by fluorescent staining results showing elevated ROS levels, reduced GSH content, and single-cell transcriptomic data revealing transcriptional suppression of HSPE1, ROMO1, and GSTM3. Meanwhile, PA treatment impaired mitochondrial function, reflected by decreased mitochondrial membrane potential and ATP levels, along with significant downregulation of mitochondrial function related genes, including NDUFA4, NDUFA6, ATP5PO, ATP5ME, COX5A, and UQCRH. These changes help explain why PA exposure reduces oocyte maturation rate and embryonic developmental potential. Notably, supplementation with 5 μM SAL effectively reversed the PA induced damage and restored oocyte developmental competence to control level to levels comparable to untreated controls. These findings suggest that SAL can restore oocyte developmental potential by mitigating the lipotoxic microenvironment induced by PA administration.