The human endometrium is highly regenerative, undergoing ~400 cycles of proliferation, differentiation, breakdown, shedding, repair and remodelling over a woman’s reproductive lifespan. Stem/progenitor cells are hypothesised to drive regeneration of this tissue. Telomerase reverse transcriptase (Tert) is up-regulated in cells that divide repeatedly and is a stem cell marker. We have recently shown mouse Tert (mTert) promoter activity in the epithelium, vasculature and immune cell population of the cycling murine endometrium, providing a model for investigating the molecular mechanisms of endometrial regeneration.
Mice expressing a green fluorescent protein reporter under the control of the mTert promoter (mTert-GFP) were subjected to a previously published mouse model of menses. Tissues were collected for histochemical analysis during the steroid-depleted breakdown and repair “window” (0hrs, 8hrs, 24hrs and 48hrs after progesterone withdrawal).
mTert promoter activity, as denoted by GFP, was identified in a temporal and spatial manner during breakdown and repair. Prior to breakdown, GFP+ cells (0hrs, 11.93±7.58 GFP+ cells/635um2) were localised to the decidualised functional stroma and were largely CD45- (pan-leukocyte marker) (12.56%±3.1 GFP+CD45+). During endometrial breakdown (8hrs) the number of mTert-GFP+ cells increased (46.13±19.58 GFP+ cells/635um2) and of these 47.3%±4.25 were CD45+.
GFP+CD45- cells were localised to residual luminal epithelium during breakdown (8hrs), repair (24hrs) and also in glandular epithelium during remodelling (48hrs). Both GFP+CD45+ and GFP+CD45- cells were localised to perivascular locations in the myometrium and along the myometrial-endometrial junction when the tissue is remodelling (48hrs).
mTert-GFP expression identifies a heterogeneous mix of cells during endometrial breakdown and repair. Further characterisation of the GFP+CD45- population is required however the presence of GFP+CD45- cells in the epithelium suggests endometrial epithelial progenitors may be activated as the tissue begins to breakdown to support repair and re-epithelialisation of the tissue.
These findings are the first evidence of oestrogen-independent driven stem/progenitor activity during “menses”.