Background
Endometrial regeneration is a highly complex, tightly controlled process. Stem/progenitor cells have been implicated in the regeneration of the tissue. Using the stem cell marker telomerase reverse transcriptase (Tert), we have shown mouse Tert (mTert) promoter activity in epithelial, endothelial and leukocyte populations in cycling mouse endometrium1. We hypothesised that cells expressing mTert may be involved in endometrial repair and remodelling in a mouse model of menses, and more specifically would contribute to luminal epithelial repair.
Methods
mTert-GFP mice were subjected to a previously published mouse model of menses2. Briefly, mice were ovariectomised, treated with oestradiol and progesterone, artificially decidualised and progesterone removed to induce a menses-like event. Tissues were collected for histochemical and flow cytometry analysis during a steroid-depleted breakdown and repair “window” (0hrs, 8hrs, 24hrs and 48hrs after progesterone withdrawal).
Results
mTert reporter activity was identified in the residual (unshed) luminal epithelium during breakdown (8hrs), repair (24hrs) and remodelling (48hrs).
Triple immunofluorescence staining for GFP/EpCAM/Ki67 revealed extensive proliferation of residual luminal epithelial cells at the 24hr time-point. mTert-GFP+ cells were observed as clusters, interspersed between Ki67+ proliferating cells and did not colocalise with Ki67.
Conclusions
These findings are the first to show putative epithelial progenitors present in repairing luminal epithelium. The presence of clusters of epithelial mTert-GFP+ cells suggests the endometrium prepares for cyclical re-epithelialisation by distributing stem/progenitor cells along its luminal surface. Epithelial mTert activity is then activated upon breakdown and shedding of the tissue to support the rapid re-epithelialisation of the endometrium.