The progesterone hormone regulates the human menstrual cycle, pregnancy, and parturition by its action via the different progesterone receptors and signaling pathways in the female reproductive tract. Progesterone actions can be exerted through classical and non-classical receptors, or even a combination of both. The former are nuclear receptors whose activation leads to transcriptional activity regulation and thus in turn leads to slower but long-lasting responses. The latter are composed of progesterone receptors membrane components (PGRMC) and membrane progestin receptors (mPRs). These receptors rapidly activate the appropriate intracellular signal transduction pathways, and they can subsequently initiate specific cell responses or even modulate genomic cell responses. This review covers our current knowledge on the mechanisms of action and the relevance of classical and non-classical progesterone receptors in female reproductive tissues ranging from the ovary and uterus to the cervix, and it exposes their crucial role in female infertility.
Our results suggest that classic P receptors (PRs) are not the only kind playing a role in the normal physiology of the endometrium. The human decidualization process could be altered by the overexpression or mislocalization of PGRMC1 in ESC.
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.
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