Phytoestrogen exposure alters endometrial stromal cells and interferes with decidualization signaling

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Authors:

Stefania Salsano, Ph.D., Silvia Pérez-Debén, M.Sc., Alicia Quiñonero, B.Sc., Roberto González-Martín, M.Sc., Francisco Domínguez, Ph.D.

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 μM.

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′:5′ 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 (ERβ) and P receptor (PR) localization were evaluated by immunofluorescence.

Result(s)

The ESC exposed to 0, 19, 20, 50, and 100 μM of genistein, daidzein, and genistein + daidzein showed a dose-dependent proliferation decrease. After 48–96 hours of culture, this reduction was significant in the presence of 50 μM of phytoestrogens versus 10 μM 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 ERβ and PR as the control dESC.

Conclusion(s)

This study reveals that high doses of phytoestrogens could affect the in vitro decidualization process.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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