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

Do bone marrow stem/progenitor cells contribute to regeneration of the mouse endometrium? (#244)

James A Deane 1 , Fiona L Cousins 1 , Caroline E Gargett 1
  1. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

The regenerative capacity of the endometrium has been attributed to stem/progenitor cells, but the origin of these cells is unclear. Reports of a bone marrow–derived contribution to endometrial stroma and epithelium [1-4], suggest a role for bone marrow stem/progenitor cells in endometrial regeneration.

Telomerase reverse transcriptase is a component of the telomerase complex and a stem cell marker. We recently used a GFP reporter for mouse telomerase reverse transcriptase promoter activity (mTert-GFP) to identify putative epithelial and endothelial stem/progenitors, and immune cells with telomerase activity in the mouse endometrium [5]. To assess whether mTert-GFP+ endometrial progenitors were derived from bone marrow, mTert-GFP bone marrow was transplanted into irradiated wild type female recipients. Microscopy of recipient endometrium 4 months after transplantation (n=8 mice, >6000 epithelial & >25,000 stromal cells examined) revealed mTert-GFP+ immune cells expressing pan-leukocyte marker CD45+, but provided no evidence of bone marrow-derived CD45- mTert-GFP+ cells in the epithelial or stromal compartments.

To address the possibility that the mTert-GFP reporter failed to mark bone marrow-derived stem/progenitors, we recreated previous studies [2&4] by transplanting wild type female recipients with bone marrow containing ubiquitously expressed chicken-beta actin-GFP. 4 months after transplantation (n=7 mice, >15,000 epithelial & >55,000 stromal cells examined) chicken-beta actin-GFP+ cells in the stromal compartment were CD45+ immune cells and no evidence of bone marrow-derived epithelial cells was observed.

We conclude it is unlikely that bone marrow stem cells give rise to endometrial epithelial or stromal cells. The misidentification of bone marrow-derived immune cells is the most probable explanation for previous reports of a bone marrow origin for these endometrial cell types.

  1. Taylor. JAMA, 2004;292:81–85.
  2. Bratincsák et al. Stem Cells 2007;25:2820–2826.
  3. Du H. et al. Stem Cells 2007;25:2082–2086
  4. Morelli et al. Biol Reprod 2013;89:7.
  5. Deane, Ong et al. Mol Hum Reprod 2016;22:272-84.