Reepithelialization of the Uterine Surface Arises from Endometrial Glands: Evidence from a Functional Mouse Model of Breakdown and Repair
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This study identified endometrial glands as the source of epithelial progenitor cells responsible for reepithelializing the uterine surface after breakdown in a mouse model.
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Abstract
The human endometrium is highly regenerative undergoing monthly cycles of growth and regression. Endometrial repair after menses is a critical component of the cycle; however, little is understood about the mechanisms behind this rapid process. Adult stem/progenitor cells identified in human and mouse endometrium may be responsible for its remarkable regenerative capacity; however, a functional role for stem/progenitor cells in menstruation is yet to be established. This study aimed to identify label retaining cells as candidate epithelial stem or progenitor cells involved in the rapid reepithelization of the uterine surface in our functional mouse model of endometrial breakdown and repair. Adult mice were pulse labeled with bromodeoxyuridine before endometrial breakdown and repair was induced. Throughout endometrial breakdown and repair, very rapid dilution of bromodeoxyuridine label was observed in the luminal epithelium, whereas label within the glandular epithelium remained constant. Importantly, glandular epithelial cells were shown to proliferate selectively in response to endometrial repair, and the majority strongly expressed estrogen receptor-alpha at this time. This is the first study to demonstrate a functionally diverse response during endometrial repair from the anatomically connected luminal and glandular epithelium and highlights the likelihood that the endometrial glands are the residence of epithelial progenitor cells contributing to reepithelialization of the uterine surface after menses.
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Cited by (22)
- Induction of menstruation in mice reveals the regulation of menstrual shedding 2025
- Endometrial regeneration and the role of the extracellular matrix: mechanisms, challenges, and future perspectives 2025
- Mechanisms of Regeneration and Fibrosis in the Endometrium 2023
- Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models 2022
- Single-cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation 2022
- Faculty Opinions recommendation of The elusive endometrial epithelial stem/progenitor cells. 2021
- Physiology of the Endometrium and Regulation of Menstruation 2020
- Stem Cells in Endometrium and Regeneration 2019
- The role of mesenchymal–epithelial transition in endometrial function 2018
- Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium 2017
- Uterine Stem Cells and Their Future Therapeutic Potential in Regenerative Medicine 2017
- Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium 2017
- Mesenchymal Stem Cells: A Promising Tool for Targeted Gene Therapy of Endometriosis 2016
- Platelets are a possible regulator of human endometrial re‐epithelialization during menstruation 2016
- Menstrual physiology: implications for endometrial pathology and beyond 2015
- Endometrial Adult/Progenitor Stem Cells: Pathogenetic Theory and New Antiangiogenic Approach for Endometriosis Therapy 2013
- Regenerating endometrium from stem/progenitor cells 2013
- Stem Cell as the Novel Pathogenesis of Endometriosis 2012
- Steroid regulation of menstrual bleeding and endometrial repair 2012
- Endometrial regeneration and endometrial stem/progenitor cells 2012
- Identification of Cells with Colony-Forming Activity, Self-Renewal Capacity, and Multipotency in Ovarian Endometriosis 2011
- Adult stem cells in the endometrium 2010
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