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Salidroside alleviates age-related metaphase II oocyte aging by enhancing mitochondrial complex I-mediated oxidative
Feimiao Wang1, Zhaoyang Wang2, Jialing Li3
1School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, China; Reproductive Medicine Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
Abstract:
The deterioration of metaphase II (MII) oocyte quality is a principal factor compromising fertility in women of advanced maternal age and a core hallmark of ovarian aging; however, effective interventions to counteract this age-related decline are currently lacking. Although salidroside (Sal) exhibits health-promoting and anti-aging properties, its protective effects against MII oocyte aging and the underlying mechanisms remain poorly understood. In this study, we demonstrated that salidroside supplementation significantly improved multiple aspects of MII oocyte quality, particularly oocyte maturation and developmental competence. Comprehensive transcriptomic analysis revealed that salidroside rescues aged oocyte quality primarily by enhancing oxidative phosphorylation (OXPHOS). This enhancement effectively reduced reactive oxygen species (ROS) accumulation, thereby attenuating DNA damage and apoptosis. Furthermore, we identified that differentially expressed genes in the OXPHOS pathway were predominantly enriched in the subunits of mitochondrial respiratory chain complex I. The protective effects of salidroside in aged MII oocytes were markedly abolished by rotenone, indicating that salidroside primarily exerts its beneficial effects through mitochondrial complex I-mediated OXPHOS. Together, our findings highlight salidroside supplementation as a promising therapeutic strategy to ameliorate age-related MII oocyte deterioration, delay ovarian aging and improve reproductive outcomes. Future studies should focus on the translational potential of this intervention for human clinical applications.
Insights
Salidroside supplementation improves egg quality in aging women by enhancing mitochondrial function and reducing oxidative stress. This natural compound shows promise for delaying ovarian aging and boosting fertility.
Area of Science:
- Reproductive biology
- Gerontology
- Mitochondrial medicine
Background:
- Oocyte quality decline is a major cause of infertility in older women.
- Aging leads to reduced oocyte maturation and developmental competence.
- Current interventions for age-related oocyte deterioration are limited.
Purpose of the Study:
- To investigate the protective effects of salidroside against age-related MII oocyte deterioration.
- To elucidate the underlying mechanisms of salidroside's action on oocyte quality.
- To assess salidroside's potential as a therapeutic strategy for improving reproductive outcomes.
Main Methods:
- Supplementation with salidroside in aged MII oocytes.
- Transcriptomic analysis to identify molecular pathways affected by salidroside.
- Assessment of oocyte maturation, developmental competence, reactive oxygen species (ROS) levels, DNA damage, and apoptosis.
- Inhibition of mitochondrial complex I with rotenone to confirm mechanism of action.
Main Results:
- Salidroside significantly improved MII oocyte maturation and developmental competence.
- Transcriptomic analysis revealed salidroside enhances oxidative phosphorylation (OXPHOS) by upregulating mitochondrial respiratory chain complex I.
- Salidroside reduced ROS accumulation, DNA damage, and apoptosis in aged oocytes.
- The beneficial effects of salidroside were abolished by rotenone, confirming its action via mitochondrial complex I.
Conclusions:
- Salidroside supplementation is a promising strategy to counteract age-related MII oocyte deterioration.
- Salidroside enhances oocyte quality by boosting mitochondrial complex I-mediated OXPHOS and reducing oxidative stress.
- This intervention may help delay ovarian aging and improve fertility outcomes in older women.
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