FIGURE 2.

Early pathogenesis of uterine fibroids The initiation of fibroids requires paracrine events among multiple cell types in the uterus. The normal myometrial cells (myocytes pictured in black) contain receptors for the steroids estrogen and progesterone (ER and PR). The uterine stem cells (orange) do not have steroid hormone receptors, but products produced by the myocytes in response to these steroids act on stem cells to promote transformation. Additionally, somatic mutations take place in the stem cells to create the phenotype of intermediate cells (blue). Of note, multiple somatic mutations can take place in a uterus, so that, as shown, the uterus commonly can have 2 fibroids with MED12 mutations and 1 with HMGA2 mutation. Fibroid cells (red) represent the transformed cell type and have increased extracellular matrix (ECM). RANKL, receptor activator of NF-κB; Wnt, wingless related integration site.