Bone marrow-derived endometrial cells express androgen receptor

Abstract

An important role for androgens in regulating endometrial proliferation and decidualization has very recently emerged. In addition, recent data demonstrate that bone marrow (BM) is a long-term source of multiple parenchymal endometrial cell types. Whether endometrial cells of bone marrow origin express androgen receptor has not been previously studied. Thus, the objective of the current study was to determine whether bone marrow-derived endometrial cells express androgen receptor (AR). Immunohistochemistry performed in uterine tissues from murine recipients of bone marrow transplant. The current study used tissues harvested in previously performed murine BM transplant experiments, in which BM cells harvested from transgenic mice which ubiquitously express Green Fluorescent Protein (GFP) were transplanted via tail vein into irradiated syngeneic female mice. BM recipients with successful hematopoietic reconstitution were hysterectomized at 12 months (n=5 animals). Immunohistochemistry was performed in uterine tissue sections of recipient mice using specific anti-AR, anti-GFP, and anti-CD45 primary antibodies. The pan-leukocyte marker CD45 was used to distinguish hematopoietic (CD45+) from nonhematopoietic (CD45-neg) endometrial cells of BM origin. Nuclei were stained with 4’,6-diamidino-2-phenylindole (DAPI). Confocal laser microscopy was used to localize and quantitate BM-derived (GFP+) cells in the endometrial parenchymal cellular compartments and to determine whether BM-derived endometrial stromal and epithelial cells express AR. Three uterine sections from each recipient animal (n=5), using 4-5 high power fields per section, were assessed. Data are expressed as mean ± SEM cell number per animal. In the endometrial stromal compartment, the mean number of cells counted was 4271.6 ± 178.4 (n=5 animals), of which 40.8% ± 3.5% express AR. BM-derived (GFP+) cells comprised 13.8% ± 2.8% of cells in the stroma, of which 24.2% ± 8.3% were nonhematopoietic (CD45-neg) stromal cells. 24.2% ± 12.7% of BM-derived, nonhematopoietic (CD45-neg) endometrial stromal cells expressed AR. In contrast to the stromal compartment, BM-derived cells comprised only 0.3% ± 0.1% cells in the LE compartment and 1.0% ± 0.2% of cells in the GE compartment. Of the few epithelial compartment cells derived from BM, 11.2% ± 8.1% in the LE and 39.9% ± 17.9% in the GE were nonhematopoietic, BM-derived epithelial cells. Of these, none expressed AR. BM-derived cells engraft the endometrial stromal compartment to a much greater degree than the epithelial compartments, implicating a potential role for these cells in decidualization. That a substantial number of BM-derived endometrial stromal cells express AR supports a role for these cells in androgen-regulated endometrial functions, such as proliferation and/or decidualization.