The effect of metformin on estrogen induced endometrial proliferation in obese and lean Zucker rats.
(3A) Effect of metformin on pro-proliferative and anti-proliferative genes expression in the rat endometrium. The transcript level of c-myc (a), c-fos (b), RALDH2 (c), and SFRP4 (d) in the endometrium from ovariectomized Zucker fa/fa rats and their lean littermates was tested by RT-qPCR. Each sample was assayed in triplicate plus a -RT control. The number of transcript molecules in 20 ng total RNA were normalized to and expressed as the percentage of 18SrRNA (n = 17-20). * p<0.025, Lean E2 vs. obese E2; # p<0.001, obese E2 vs. obese E2+metformin.
(B) Effect of metformin on endometrial cell proliferation in Zucker obese and lean rats. The proliferative effect of estrogen on the endometrium is reported as a ratio of BrdU labeled endometrial cells per 200 endometrial epithelial cells. BrdU (100mg/kg) was injected intraperitoneally into rats 90 minutes before they were sacrificed. Uterine tissue sections were stained with anti-BrdU antibody. The average number of positively stained cells in 10 high-power microscopic fields were counted per slide (n=17-26/group). Scale bar=200 μm.