Glycolytic Reprogramming in Uterine Fibroids: Genetic, Transcriptomic, Proteomic, and Metabolomic Insights

Area of Science:

• Reproductive biology
• Oncology
• Metabolic research

Background:

• Uterine fibroids (leiomyomas) are common benign tumors affecting 70-80% of women of reproductive age.
• The exact causes of uterine fibroids remain unclear despite their high prevalence.
• Existing research links genetic factors like fumarate hydratase (FH) deficiency and MED12 mutations to fibroid development.

Purpose of the Study:

• To review the distinct metabolic features of uterine fibroids.
• To highlight the role of glycolytic reprogramming in fibroid pathogenesis.
• To explore potential therapeutic targets based on metabolic alterations.

Main Methods:

• Review of existing genetic, transcriptomic, proteomic, and metabolic studies.
• Analysis of fibroid-specific metabolic adaptations.
• Examination of signaling pathways involved in fibroid growth and fibrosis.

Main Results:

• Uterine fibroids display unique metabolic reprogramming, with a significant role for altered glycolysis.
• Glycolysis supports fibroid biosynthetic demands, proliferation, extracellular matrix (ECM) production, survival, and fibrosis.
• Key pathways like transforming growth factor-beta (TGF-β) and Wnt/β-catenin signaling are implicated in fibroid pathogenesis via glycolytic reprogramming.

Conclusions:

• Metabolic reprogramming, especially glycolytic adaptation, is a critical factor in uterine fibroid development and fibrosis.
• Regulators such as HIF-1α, mTOR, and PI3K/Akt may sustain the fibrotic phenotype by linking ECM production to metabolic programming.
• Further research in uterine-specific models and larger cohort studies is needed for mechanistic investigation and therapeutic targeting.