Uterine stem cells

The uterus is essential for reproduction in most mammalian species and is arguably the most naturally plastic organ in terms of tissue remodeling in mammals. Histologically, the uterus is divided into the endometrium and the outer smooth muscle layer called the myometrium. The endometrium harbors epithelial (glandular and luminal) and fibroblast-like stromal cells, and is separated physiologically into the functionalis (inner most region nearest the lumen) and basalis layers. The key morphological changes that the uterus undergoes are in response to cyclical hormonal cues from the ovary and from the implanting embryo during pregnancy. During menses and following parturition, the functionalis layer of the endometrium regresses and is lost in primates and must be replaced. During pregnancy, the wet weight of the uterus increases 10-fold largely due to myometrial smooth muscle cell hypertrophy and hyperplasia. We believe that the remodeling of the uterus in response to these stimuli and its return to a basal state requires adult stem (or progenitor) cells that reside in the individual endometrial and myometrial compartments. Furthermore, we suspect that several pathological conditions, such as endometrial cancer, endometriosis, and leiomyomata (i.e., uterine fibroids), can be attributed to dysregulation of these same stem cells, or are derived from committed cells that acquire stem-like features. We will review uterine development and its response to hormonal cycling and pregnancy, uterine neoplasia, and the evidence for a role for uterine stem cells in these settings.