Title: THE BONE MORPHOGENETIC PROTEIN 2 (BMP2) SIGNALING PATHWAY PLAYS A CRITICAL ROLE IN UTERINE STROMAL DIFFERENTIATION IN THE MOUSE AND THE HUMAN
Abstract: The steroid hormones progesterone (P) and estrogen (E) act in concert to control uterine competency for embryo implantation. A primary role of P is to induce differentiation of the endometrial stromal cells into decidual cells that maintain an environment conducive to the growth and development of the implanting embryo. Our recent studies have shown that BMP2, a member of the TGF beta superfamily, is rapidly induced in response to P and progesterone receptor (PR) in the mouse uterus during decidualization. We have analyzed the role of BMP2 in uterine stromal cell differentiation using primary cultures of these cells isolated from pregnant mouse uterus. We found that addition of recombinant BMP2 to undifferentiated stromal cultures markedly advanced the differentiation program by stimulating the Smad signaling pathway. Conversely, siRNAmediated down-regulation of BMP2 expression in these cells efficiently blocked the differentiation process, as indicated by the loss of expression of selected markers of the decidual state. In more recent studies, we investigated the expression of BMP2 in human endometrial stromal cells during in vitro decidualization. Stromal cells isolated from human endometrial biopsies obtained from normal fertile women in the proliferative stage of the menstrual cycle were placed in culture and subjected to decidualization in response to a hormonal cocktail containing P, E, and 8-bromo-cAMP (a cAMP analog). We noted a clear morphological transition of the stromal cells from a fibroblastic to an epitheloid shape with the progression of decidualization by day 6 of the culture. We also observed the induction of classical decidualization biomarkers, PRL and IGFBP-1, during the in vitro decidualization process. We observed a marked enhancement in the expression of BMP2 in human stromal cells in response to the hormone cocktail. More importantly, addition of exogenous BMP2 along with P, E, and 8-bromo-cAMP to these stromal cultures led to a dramatic induction in the levels of PRL and IGFBP-1 mRNAs. Taken together, our results indicated that BMP2 is induced in the mouse and human endometrium during decidualization and plays a critical role in this differentiation program. (platform)
Publication Year: 2007
Publication Date: 2007-07-01
Language: en
Type: article
Indexed In: ['crossref']
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