The regenerative properties of the endometrium have been attributed to epithelial and stromal stem/progenitor cells. Wnt signalling is a developmental and stem cell pathway that is important for normal uterine development. In the intestine, Wnt signalling maintains a niche containing epithelial stem cells expressing the Wnt target gene Lgr5. Lgr5 is a stem cell marker in other organs including the hair follicle and stomach.
We investigated whether Wnt signalling and Lgr5 expression also defines a niche containing stem/progenitor cells in the endometrium. An Lgr5-GFP reporter mouse was used to determine whether Lgr5 expressing cells were present in the endometrium of adult mice undergoing an estrous cycle. Immunofluorescence for the Wnt target gene Axin-2 was used to detect Wnt activation in mouse and human endometrium.
Lgr5-GFP was not expressed in the adult mouse endometrium, but was readily detected at sites of known Lgr5 expression such as the intestinal crypt and ovarian surface epithelium. The Wnt target gene Axin-2 was widely expressed in mouse and human endometrial epithelium, without any restricted localisation that might be indicative of a stem cell niche. In the human endometrium, Axin-2 was prominent in the epithelium of differentiated functionalis endometrium. Axin-2 was not highly expressed in the basal N-cadherin positive glands that are enriched for cells possessing the stem cell property of clonogenic growth.
We conclude that endometrial Wnt activity is linked to epithelial differentiation rather than stem/progenitor cell function. Endometrial epithelial stem/progenitor cell populations are likely to be maintained by mechanisms distinct from the Wnt/Lgr5 system that operates in the intestine and other organs.