Complex networks of multiple factors in the pathogenesis of uterine leiomyoma

Objective: To summarize the information regarding pathogenetic factors of leiomyoma formation and growth, and to make a simple integrated pathogenetic view of this tumor for further thinking to establish new therapeutic options. Design: PubMed and Google Scholar searches were conducted to identify the relevant studies on pathogenesis of uterine leiomyoma, which are hereby reviewed and discussed. Setting: Academic medical center. Patient(s): Not applicable. Intervention(s): Not applicable. Main Outcome Measure(s): Not applicable. Result(s): To date, the pathogenesis of uterine leiomyomas is not well understood. However, genetic alterations (especially MED12 and HMGA2) and involvement of epigenetic mechanisms (DNA methylation, histone modifications, and microRNA) in leiomyoma provide the clue of initiator of this tumor. Estrogens and P are considered as promoters of leiomyoma growth, and growth factors, cytokines, and chemokines are thought to be as potential effectors of estrogens and P. Extracellular matrix components are a major structural part of leiomyoma tissue that are abnormally orientated and can modify mechanical stress on cells, which leads to activation of internal mechanical signaling and may contribute to leiomyoma growth. Conclusion(s): Besides many genetics and epigenetic factors, the important link among the sex steroids, growth factors, cytokines, chemokines, and extracellular matrix and their involvement in cell proliferation, fibrotic processes, apoptosis, and angiogenesis are implicating a complex network in leiomyoma formation and growth. Those findings could provide information to establish future therapeutic options for the management of this tumor.