Hypoxia: the driving force of uterine myometrial stem cells differentiation into leiomyoma cells.

We propose that stem cells that display specific phenotypic and functional characteristics exist in human uterine myometrium. Under hypoxic circumstances, estrogen signaling pathways in certain myometrial stem cells are aberrantly activated, which leads to continuous differentiation of this portion of cells into leiomyoma cells. This process also protects the cells from undergoing physiological apoptotic or dedifferentiation. Therefore, we summarized some evidences for our bases and hypothesize that hypoxia may be the key contributor to the pathogenesis of leiomyoma through aberrant estrogen pathway activation of myometrial stem cells.