Endometrial and decidual stromal precursors show a different decidualization capacity

in Reproduction

Correspondence should be addressed to E G Olivares; Email: engarcia@ugr.es
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Endometrial stromal cells (EnSCs) and decidual stromal cells (DSCs) originate from fibroblastic precursors located around the vessels of the human nonpregnant endometrium and the pregnant endometrium (decidua), respectively. Under the effect of ovarian or pregnancy hormones, these precursors differentiate (decidualize), changing their morphology and secreting factors that appear to be essential for the normal development of pregnancy. However, the different physiological context – that is, non-pregnancy vs pregnancy – of those precursors (preEnSCs, preDSCs) might affect their phenotype and functions. In the present study, we established preEnSC and preDSC lines and compared the antigen phenotype and responses to decidualization factors in these two types of stromal cell line. Analyses with flow cytometry showed that preEnSCs and preDSCs exhibited a similar antigen phenotype compatible with that of bone marrow mesenchymal stem/stromal cells. The response to decidualization in cultures with progesterone and cAMP was evaluated by analyzing changes in cell morphology by microscopy, prolactin and IL-15 secretion by enzyme immunoassay and the induction of apoptosis by flow cytometry. In all four analyses, preDSCs showed a significantly higher response than preEnSCs. The expression of progesterone receptor (PR), protein kinase A (PKA) and FOXO1 was studied with Western blotting. Both types of cells showed similar levels of PR and PKA, but the increase in PKA RI subunit expression in response to decidualization was again significantly greater in preDSCs. We conclude that preEnSCs and preDSCs are equivalent cells but differ in their ability to decidualize. Functional differences between them probably derive from factors in their different milieus.

Supplementary Materials

    • Supplemental Figure 1. Characteristics of MSC lines. A) Changes in MSC morphology from a fibroblastic to a rounder shape after 14 days incubation with P4 and cAMP. Determination by RT-PCR (B) and ELISA (C) of PRL production by MSCs after 14 days of treatment with P4 and cAMP. A preDSC line was used as a positive control. In (B), β2MG was used as a control for RNA input. Panels A and B show the results for a single experiment representative of three separate assays with different cell lines. Error bars in C show the SEM of all three experiments.
    • Supplemental Figure 2. Comparative analysis of preEnSCs from menstrual blood and from endometrial biopsy. A) Expression of different cell surface antigens analyzed by flow cytometry in preEnSC cell lines derived either from menstrual blood or endometrial biopsy. B) PRL secretion by preEnSCs from menstrual blood and endometrial biopsy at 28 days incubation with P4 and cAMP. C) Induction of apoptosis upon incubation without (undifferentiated) or with P4 and cAMP for 28 days. Error bars show the SEM of at least five independent experiments with different cell lines.

 

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