Uterine Fibroids: Origin and Composition
Uterine fibroids are benign smooth muscle cell (SMC) tumors of the myometrium characterized by increased smooth muscle cell proliferation and collagen deposition. 1
Cellular Origin and Composition
- Fibroids (leiomyomas) are monoclonal tumors that originate from the smooth muscle cells of the uterine myometrium 1
- They are well-vascularized benign neoplasms with increased extracellular matrix production 1
- These tumors display characteristics of well-differentiated uterine smooth muscle cells similar to those found in pregnant myometrium 1
Pathophysiological Features
- Fibroids exhibit dysregulation of growth factors and their receptors, particularly transforming growth factor-β (TGF-β) 1
- TGF-β3 is significantly elevated (5-fold higher) in leiomyomas compared to normal myometrium 1
- Several growth factors have been identified in both normal myometrium and fibroid tissue:
- Platelet-derived growth factor
- Heparin-binding epidermal growth factor
- Hepatoma-derived growth factor
- Basic fibroblast growth factor 1
Genetic and Molecular Characteristics
- Heterogeneous cytogenetic abnormalities are associated with fibroid development 1
- Specific translocations, such as chromosomal 12:14 translocation, result in abnormal expression of high mobility group IC gene 1
- Loss of the tuberous sclerosis 2 gene has been linked to leiomyoma development 1
- Fibroids display an estrogen-driven pattern of gene expression similar to that seen in normal myometrium during pregnancy 1
Hormonal Influence
- Fibroids exhibit hypersensitivity to sex steroid hormones 1
- This hormonal sensitivity prevents fibroid cells from responding to normal apoptotic signals 1
- Unlike normal myometrial cells that can undergo apoptosis or dedifferentiation after pregnancy, leiomyoma cells persist in a proliferative state 1
- This explains why fibroids occur predominantly during reproductive years when estrogen levels are highest 1
Clinical Significance
- Uterine fibroids are the most common gynecological neoplasm in women 1
- They affect approximately 20-25% of women during reproductive years 1
- Fibroids are the leading cause of hysterectomies among premenopausal women in the United States 1
- They can cause abnormal uterine bleeding, pelvic pressure, pain, and reproductive issues 2
Understanding the cellular origin and composition of uterine fibroids is essential for developing targeted therapeutic approaches that can address the underlying pathophysiology rather than just managing symptoms.