2. Academic Validation
  3. Mogroside V restores glycolytic function via LDHA promoter demethylation independent of alternative splicing in PCOS granulosa cells

Mogroside V restores glycolytic function via LDHA promoter demethylation independent of alternative splicing in PCOS granulosa cells

  • J Steroid Biochem Mol Biol. 2025 Jul 28:254:106839. doi: 10.1016/j.jsbmb.2025.106839.
Shuai Li 1,  Jiaxin Wu 1,  Renhong Lu 1,  Benliang Zhou 1,  Hongpeng Dai 1,  Zhen Zhang 1,  Xiaogan Yang 1,  Xingwei Liang 2
Affiliations

Affiliations

  • 1 College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China; Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, Guangxi University, Nanning, Guangxi 530004, China.
  • 2 College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China; Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, Guangxi University, Nanning, Guangxi 530004, China. Electronic address: xwliang@gxu.edu.cn.
PMID: 40738262 DOI: 10.1016/j.jsbmb.2025.106839
Abstract

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by metabolic dysfunction. This study investigated whether Mogroside V (MV) ameliorates hyperandrogenism-induced glycolytic dysfunction in testosterone (TES)-treated KGN cells. KGN cells treated with 150 µM TES exhibited significantly reduced viability, decreased lactate production, and increased pyruvate levels, which were reversed by 60 µM MV. Transcriptomic analysis revealed that TES dysregulated gene expression associated with alternative splicing (AS) and glycolytic pathways, while MV normalized glycolysis-related genes (LDHA, PKM) without affecting AS events. Although TES upregulated splicing factors HNRNPH3 and SRSF1, MV restored the expression of HNRNPH3 and SRSF1 without inducing aberrant splicing. Mechanistically, MV significantly reduced TES-induced hypermethylation of the LDHA promoter, thereby restoring LDHA mRNA and protein expression. MV mitigates PCOS-associated metabolic dysfunction primarily through LDHA promoter demethylation, independent of alternative splicing regulation. This study highlights MV as a natural compound with epigenetic regulatory potential for PCOS therapy.

Keywords

Alternative Splicing; DNA methylation; Glycolysis; Mogroside V; Polycystic ovary syndrome.

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