Isoflavones regulate secretion of leukemia inhibitory factor and transforming growth factor β and expression of glycodelin in human endometrial epithelial cells

Abstract

Isoflavones have attracted much attention due to their association with health benefits. However, comprehensive understanding of the beneficial impacts of isoflavones on uterine biology at the molecular level remains unexplored. Therefore, we tested the hypothesis that isoflavones, including isoflavones aglycones AglyMax-70, genistein, daidzein and equol within the range of the plasma concentration displays disparate bioavailability in regulating the secretion of Leukaemia inhibitory factor (LIF), transforming growth factor β (TGF-β), and expression of glycodelin in Ishikawa cells and in normal human endometrial epithelial cells. Prospective, in vitro experimental study. Human endometrial epithelial Ishikawa cells obtained from the Human Science Research Resources Bank (Osaka, Japan), the normal human endometrial epithelial cells were isolated from endometrium tissues. We used epithelial cells in culture after the first passage. We tested the isoflavones aglycones AglyMax-70, genistein, daidzein and equol within the range of the plasma concentration displays disparate bioavailability in regulating the secretion of LIF, TGF-β, and expression of glycodelin in Ishikawa cells and in normal human endometrial epithelial cells. In the present study, isoflavones aglycones AglyMax-70, genistein, and equol, but not daidzein, within the range of plasma concentration displays bioavailability in regulating secretion of LIF and TGF-β in Ishikawa cells, which was blocked by an estrogen receptor antagonist ICI 182 780, MEK1/2 inhibitor PD98059, and p38 MAP kinase inhibitor SB203580. We also found that AglyMax-70 and genistein increased in cyclic AMP release and expression of glycodelin protein in Ishikawa cells assayed by using Western blot and immunochemistrical staining. The MEK1/2 inhibitor PD98059 and PKA inhibitor H89, but not SB203580, attenuated this glycoprotein expression. Moreover, isoflavones aglycones AglyMax stimulated LIF, TGF-β secretion and glycodelin expression in separated primary endometrial epithelial cells at the follicular phase or luteal phase from health subject donors. Overall, the present in vitro studies demonstrated that isoflavones aglycones elevated the secretion of LIF and TGF-β and induced expression of glycodelin in Ishikawa cells and isolated human primary endometrial epithelial cells. Thus soy isoflavones aglycones acting as a dietary supplement may have benefit for uterine biology and early pregnancy.