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Updated: Aug 6, 2026
A Modified Technique for Inducing Polycystic Ovary Syndrome in Mice
Published on: July 5, 2024
Disulfidptosis in PCOS pathogenesis: Multi-omics identification of LRPPRC as a diagnostic biomarker and therapeutic
Lele Ling1, Shiyu Zhang1, Dongyao Zhang1
1Department of Obstetrics and Gynecology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Abstract:
Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunction, insulin resistance, oxidative stress, and metabolic abnormalities, yet the role of disulfidptosis in granulosa cell injury remains unclear. Here, integrated single-cell and bulk transcriptomic analyses identified granulosa cells as the primary disulfidptosis-associated cell type in the PCOS follicular microenvironment. Disulfidptosis-related genes, including leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), NDUFS1, and OXSM, were significantly downregulated and associated with mitochondrial dysfunction and redox imbalance. A diagnostic model achieved an AUC of 0.867, while Mendelian randomization identified LRPPRC as a protective factor for PCOS. Functionally, LRPPRC deficiency under glucose deprivation induced NADPH depletion, F-actin collapse, and granulosa cell death, which was rescued by 2-mercaptoethanol but not by apoptosis, ferroptosis, or necroptosis inhibitors. In vivo, LRPPRC overexpression improved follicular development and hormonal balance in PCOS mice. These findings identify LRPPRC-mediated disulfidptosis as a potential biomarker and therapeutic target in PCOS.
Insights
Polycystic ovary syndrome (PCOS) involves granulosa cell injury, where disulfidptosis plays a key role. Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) deficiency worsens PCOS, suggesting LRPPRC-mediated disulfidptosis as a therapeutic target.
Area of Science:
- Reproductive biology
- Cellular and molecular biology
- Metabolic disease research
Background:
- Polycystic ovary syndrome (PCOS) presents with reproductive dysfunction, insulin resistance, and metabolic issues.
- The specific role of disulfidptosis in granulosa cell injury within PCOS remains largely unknown.
- Granulosa cells are crucial for follicular development and oocyte maturation.
Purpose of the Study:
- To investigate the role of disulfidptosis in granulosa cell injury in PCOS.
- To identify key genes and pathways involved in disulfidptosis in the PCOS follicular microenvironment.
- To evaluate the diagnostic and therapeutic potential of disulfidptosis-related factors in PCOS.
Main Methods:
- Integrated single-cell and bulk transcriptomic analyses were performed on PCOS patient samples.
- Gene expression levels of disulfidptosis-related genes (LRPPRC, NDUFS1, OXSM) were analyzed.
- A diagnostic model was developed, and Mendelian randomization was used to identify causal genetic factors.
- Functional assays were conducted using cell cultures under glucose deprivation, and in vivo studies were performed in PCOS mouse models.
Main Results:
- Granulosa cells were identified as the primary cell type associated with disulfidptosis in PCOS.
- Downregulation of LRPPRC, NDUFS1, and OXSM correlated with mitochondrial dysfunction and redox imbalance.
- A diagnostic model achieved an AUC of 0.867, and LRPPRC was identified as a protective factor for PCOS.
- LRPPRC deficiency induced granulosa cell death via disulfidptosis, which was rescued by specific inhibitors.
- Overexpression of LRPPRC in mice improved follicular development and hormonal balance.
Conclusions:
- Disulfidptosis, particularly LRPPRC-mediated, is implicated in granulosa cell injury in PCOS.
- LRPPRC acts as a protective factor against PCOS development and progression.
- LRPPRC-mediated disulfidptosis represents a potential diagnostic biomarker and therapeutic target for PCOS.