Label-retaining, putative mesenchymal stem cells contribute to repair of the myometrium during uterine involution.

Uterine remodeling during pregnancy and postpartum uterine involution are two fundamental, dynamic processes that are required for successful propagation of eutherian species. The uterus can increase in size up to 40-fold during pregnancy, which is largely attributed to expansion of the myometrium by hyperplasia and hypertrophy. Following pregnancy, the uterus repairs the remodeled or "damaged" tissue during uterine involution. Little is known about this repair process, particularly the role of mesenchymal stem/progenitor cells. The objective of this study was to identify and characterize putative mesenchymal stem/progenitor cells in the murine myometrium using a combination of label-retention and mesenchymal stem cell (MSC) marker expression and a pregnancy and uterine involution model. Tet-off transgenic mice with the Cre-lox system were used to specifically label mesenchymal cells (i.e. myometrial and endometrial stromal cells) within the uterus while avoiding other cell types (e.g. epithelial, immune and endothelial cells) to identify slowly dividing cells and assess their stem cell qualities. We identified myometrial label-retaining cells (LRCs) that persisted for at least three months, expressed CD146 and CD140b (MSC markers), and proliferated at a higher rate during uterine involution compared to non-labeled cells. The LRCs did not appear to express either ERα or PR, nor did the number of LRCs change at different estrous stages or in response to exogenous estradiol or progesterone administration, suggesting that LRCs were not involved in normal estrous cycling. The results from this study provide important insight into putative stem/progenitor cells in the myometrium and their possible role in uterine physiology.