Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

mTert promoter activity identifies putative stem/progenitor cells and immune cells in a mouse model of menses and endometrial repair (#54)

Fiona L Cousins 1 2 , James A Deane 1 2 , Caroline E Gargett 1 2
  1. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VICTORIA, Australia
  2. Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia

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”.