Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Mouse telomerase reverse transcriptase expression identifies endometrial progenitors with epithelial differentiation potential (#357)

James A Deane 1 , David T Breault 2 , Caroline E Gargett 1
  1. MIMR-PHI Institute, Clayton, VIC, Australia
  2. Division of Endocrinology, Children's Hospital , Harvard Medical School, Boston, MA, USA

The role of epithelial and stromal stem/progenitor cells in endometrial regeneration is not clear due to the lack of a traceable marker for these populations. Telomerase reverse transcriptase (Tert) is the rate limiting component of the telomerase complex that allows stem cells to avoid senescence during repeated cycles of cell division. We are using transgenic reporter mice to investigate whether mouse telomerase reverse transcriptase (mTert) expression marks endometrial stem/progenitor cells in the mouse endometrium. GFP under the control of the mTert promoter (mTert-GFP) identifies a rare population of intrinsic (CD45 negative) endometrial stromal cells in developing and adult mice. Rare focal regions of epithelial mTert-GFP expression are observed in both the glandular and luminal epithelium of the endometrium in adult mice. Endometrial mTert-GFP cells are distinct from stromal and epithelial label-retaining cells previously identified in mouse endometrium. Stromal mTert-GFP cells do not express estrogen receptor-α but epithelial mTert-GFP cells are estrogen receptor-α positive. Epithelial mTert-GFP cells are not slow cycling and display a level of proliferation comparable to mTert negative epithelium. Endometrial stromal and epithelial mTert-GFP cells are reduced following ovariectomy, demonstrating that ovarian hormones regulate endometrial mTert populations. Inducible Cre recombinase under the control of the mTert promoter has been used to identify the contribution of mTert lineage cells to endometrial regeneration. Tracing of mTert-derived cells during postnatal development shows that the mTert lineage is largely confined to the stroma of prepubertal endometrium, but contributes extensively to glandular and luminal epithelium in the endometrium of adult cycling mice. In adult mice, the removal of ovarian hormones by ovariectomy blocks the epithelial contribution of the mTert lineage. Our data suggest that epithelial structures of the adult cycling endometrium originate from an mTert expressing stromal stem/progenitor cell that undergoes mesenchymal-to-epithelial transition during cyclic endometrial regeneration.