Phytoestrogen exposure alters endometrial stromal cells and interferes with decidualization signaling

Abstract

Objective: To investigate whether phytoestrogens (genistein and daidzein) alter in vitro decidualization of human endometrial stromal cells (ESCs). Design: Isolated primary ESCs were exposed to phytoestrogens and decidualized in vitro. Setting: Academic fertility center. Patient(s): Twenty fertile oocyte donors attending the IVI Valencia clinic. Intervention(s): Treatment of ESC with phytoestrogens at 0, 10, 20, 50, and 100 mM. Main Outcome Measure(s): The ESC proliferation was analyzed by MTS assay. In vitro decidualization was induced in the presence of phytoestrogens by medroxyprogesterone acetate/cyclic adenosine 3 0 :5 0 monophosphate and evaluated by prolactin (PRL) ELISA and F-actin immunostaining. The Ki67 proliferative marker was analyzed by immunofluorescence. The ESC apoptosis was assessed by annexin V/propidium iodide detection using flow cytometry. Estrogen (ERb) and P receptor (PR) localization were evaluated by immunofluorescence. Result(s): The ESC exposed to 0, 19, 20, 50, and 100 mM of genistein, daidzein, and genistein þ daidzein showed a dose-dependent proliferation decrease. After 48-96 hours of culture, this reduction was significant in the presence of 50 mM of phytoestrogens versus 10 mM untreated ESC. The ESC decidualized in the presence of phytoestrogens did not rearrange their cytoskeletons and showed a significant decrease in PRL secretion compared with untreated decidualized ESCs (dESCs). However, phytoestrogens did not alter proliferative status or the percentage of viable/apoptotic cells in dESC compared with untreated dESC. During decidualization, phytoestrogens induced the same nuclear translocation of ERb and PR as the control dESC. Conclusion(s):This study reveals that high doses of phytoestrogens could affect the in vitro decidualization process.

Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats

“…However, VFE treatment ameliorated uterine atrophy and tissue weight loss observed in untreated OVX rats. A previous study has shown that phytoestrogens such as genistein and daidzein can alter endometrial stromal cells and interfere with decidualization signaling [38]. We also confirmed that VFE increased the protein expression of ER-α and blood estradiol levels.…”

Estrogenic Pastures: A Source of Endocrine Disruption in Sheep Reproduction

“…In rats, phytoestrogen exposure during the fetal and early neonatal stage is associated with long term alterations to the estrous cycle after the exposed individuals reach puberty, with prolonged suppression of ovarian cycling ( 117 ) and inhibition of LH secretion ( 118 ). Neonatal exposure to genistein might create a more hostile uterine environment that is less capable of supporting embryo implantation ( 103 , 119 ). In addition to these reproductive consequences, in utero exposure to estrogenic compounds also impairs immune function in rats ( 120 ), increases the incidence of cancerous lesions in the uterus ( 121 , 122 ), and impairs the development of estrogen-sensitive organs, particular secondary sex organs ( 123 , 124 ).…”

Phytoestrogens for the Management of Endometriosis: Findings and Issues

“…However, in primary cultures of human endometrial stromal cells, genistein (1 nmol/L to 1 mmol/L) upregulated the expression of aromatase activity and increase the aromatase activity, suggesting that genistein could modify the natural course of endometriosis thorough affecting local estrogen biosynthesis. Also in endometrial stromal primary cultures, Salsano et al observed that 10, 20, 50, and 100 µmol/L of genistein, daidzein, or genistein + daidzein inhibited cell proliferation and prolactin secretion, and induced in vitro decidualization, in a dose-dependent manner [85]. Srisomboon et al demonstrated that in the primary culture of porcine endometrial epithelial cells, genistein and daidzein enhanced β-defensins (PBD)-2 expression and PBD-2 and PBD-3 secretion [86].…”