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TISSUE-SPECIFIC STEM CELLS

Adult Mouse Myometrial Label-Retaining Cells Divide in Response to Gonadotropin Stimulation

^aPediatric Surgical Research Laboratories, Department of Surgery,
^bVincent Center for Reproductive Biology, Department of Obstetrics, Gynecology and Reproductive Biology, and
^cFlow Cytometry Laboratory, Department of Pathology and The Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

Key Words. Mouse myometrium • Stem cell niche • Label-retaining cells • Mesenchymal stem cell • Myometrial stem cell

Correspondence: Jose Teixeira, Ph.D., Vincent Center for Reproductive Biology/Thier 913, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.

Received on April 10, 2006; accepted for publication on January 29, 2007.

First published online in STEM CELLS EXPRESS  February 8, 2007.


Conditional deletion of β-catenin in the Müllerian duct mesenchyme results in a degenerative uterus characterized by replacement of the myometrial smooth muscle with adipose tissue. We hypothesized that the mouse myometrium houses somatic smooth muscle progenitor cells that are hormonally responsive and necessary for remodeling and regeneration during estrous cycling and pregnancy. We surmise that the phenotype observed in β-catenin conditionally deleted mice is the result of dysregulation of these progenitor cells. The objective of this study was to identify the mouse myometrial smooth muscle progenitor cell and its niche, define the surface marker phenotype, and show a functional response of these cells to normal myometrial cycling. Uteri were labeled with 5-bromo-2'-deoxyuridine (BrdU) and chased for up to 14 weeks. Myometrial label-retaining cells (LRCs) were observed in the myometrium and stroma throughout the chase period. After 12 weeks, phenotypic analysis of the LRCs by immunofluorescence demonstrated that the majority of LRCs colocalized with -smooth muscle actin, estrogen receptor-, and β-catenin. Flow cytometry of myometrial cells identified a myometrial Hoechst 33342 effluxing "side population" that expresses MISRII-Cre-driven YFP. Functional response of LRCs was investigated by human chorionic gonadotropin stimulation of week 12 chase mice and demonstrated sequential proliferation of LRCs in the endometrial stroma, followed by the myometrium. These results suggest that conventional myometrial regeneration and repair is executed by hormonally responsive stem or progenitor cells derived from the Müllerian duct mesenchyme.

Disclosure of potential conflicts of interest is found at the end of this article.

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