Identification of label-retaining perivascular cells in a mouse model of endometrial decidualization, breakdown, and repair

The human endometrium is incredibly dynamic, undergoing monthly cycles of growth and regression during a woman s reproductive life. Endometrial repair at the cessation of menstruation is critical to re-establishment of a functional endometrium receptive for embryo implantation, however little is understood about the mechanisms behind this rapid and highly efficient process. This study utilized a functional mouse model of endometrial breakdown and repair to assess changes in endometrial vasculature that accompany these dynamic processes. Given adult endometrial stem/progenitor cells identified in human and mouse endometrium are likely contributors to the remarkable regenerative capacity of endometrium, we also assessed label retaining cells as candidate stromal stem/progenitor cells and examined their relationship with endometrial vasculature. Newborn mouse pups were pulse-labeled with bromodeoxyuridine (BrdU) and chased for 5 weeks, before decidualization, endometrial breakdown and repair were induced by hormonal manipulation. Mean vessel density did not change significantly throughout breakdown and repair, however significantly elevated endothelial cell proliferation was observed in decidual tissue. Stromal LRC were identified throughout breakdown and repair, with significantly fewer observed during endometrial repair than before decidualization. A significantly higher percentage of LRC were associated with vasculature during repair than before decidualization, and a proportion were undergoing proliferation, indicative of their functional capacity. This study is the first to examine the endometrial vasculature and candidate stromal stem/progenitor cells in a functional mouse model of endometrial breakdown and repair and provides functional evidence suggesting that perivascular LRC may contribute to endometrial stromal expansion during the extensive remodeling associated with this process.