Figure 2.

Leiomyoma development. Genetic aberrations involving genes such as HMGA2, MED12 and FH may initiate unregulated cell proliferation of myometrial stem cells. Cyclic menstrual contractions of the myometrium result in periodic hypoxia/ischemia, which may lead to differentiation of myometrial stem cells into SMCs. Continued uncontrolled proliferation of mutated stem cell derived SMCs would result in foci of MMH. The effects of gonadal steroids in combination with the chronic hypoxia associated with the rapidly expanding MMH cell mass would stimulate local angiogenic growth factor expression. These, in turn, would promote continued cell proliferation, and ECM deposition, and provide a vascular support to the growing myometrial cell mass, resulting in leiomyoma formation. SMCs, smooth-muscle cells; HMGA2, high-mobility group AT-hook 2 protein; MED12, mediator subunit complex 12; FH, fumarate hydratase; MMH, myometrial hyperplasia; ECM, extracellular matrix; ADM, adrenomedullin.