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Role of Label-Retaining Cells in Estrogen-Induced Endometrial Regeneration

Abstract

Candidate stem/progenitor cells have been identified in mouse endometrium as label-retaining cells (LRCs). The role of endometrial stem/progenitor cells in initiating estrogen-stimulated endometrial growth in prepubertal and cycling mice was investigated following a single 17β-estradiol (E2) injection in bromodeoxyuridine (BrdU)-labeled and -chased (LRC), ovariectomised mice. Proliferating (BrdU+/Ki-67+) and mitotic (BrdU+/PH3+) epithelial LRCs were first detected in prepubertal mice 8 hours following E2 treatment, initiating the proliferative response. In contrast, all epithelial LRCs and 16% of epithelial cells in cycling mice proliferated within 2 hours. In cycling mice, 12% of stromal LRCs initiated a proliferative response 8 hours after E2. Proliferating epithelial LRCs and most stromal LRCs (85%) lacked estrogen receptor-α (ESR1). These findings suggest that endometrial epithelial LRCs function as stem/progenitor cells by receiving proliferative signals from neighboring ESR1+ niche cells to initiate the growth of the epithelium during development, while mature epithelial cells may undergo self-replication in cycling endometrium.

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Correspondence to Caroline E. Gargett PhD.

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Chan, R.W.S., Kaitu’u-Lino, T. & Gargett, C.E. Role of Label-Retaining Cells in Estrogen-Induced Endometrial Regeneration. Reprod. Sci. 19, 102–114 (2012) doi:10.1177/1933719111414207

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Keywords

  • adult stem cells
  • endometrium
  • mouse
  • estrogen
  • regeneration