Molecular Human Reproduction Vol. 2, NUMBER 3 pp. 185-193, 1996
© European Society of Human Reproduction and Embryology 1996
research-article |
Retinoic acid suppresses in-vitro decidualization of human endometrial stromal cells
1Division of Endocrinology, Children's Hospital Medical Center 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039 2Department of Obestetrics and Gynecology, University of Cincinnati Medical Center Ohio 45677, USA
To whom correspondence should be addressed at: 3To whom correspondence should be addressed
All-trans retinoic acid (RA) has potent effects on cell differentiation and gene expression. Previous studies have demonstrated that human endometrial stromal cells express mRNA for retinoic acid receptors (RARs) and cellular RA-binding protein-ll (CRABP-II). We examined whether RA regulates stromal cell differentiation (decidualization), a critical process in preparation of the uterus for blastocyst implantation. Decidualization was induced by incubating cultured stromal cells with medroxyprogesterone acetate (MPA) and oestradiol. Decidualization was defined by the induction of prolactin, insulin-like growth factor binding protein-1 (IGFBP-1), appearance of a differentiated phenotype and changes in fibronectin expression. RA treatment significantly (P<0.05) suppressed prolactin and IGFBP-1 production associated with stromal cells decidualization. The formation of differentiated cells was inhibited by RA, and consistent with maintenance of the undifferentiated phenotype, fibronectin mRNA content was -3.5-times greater than in the absence of RA. Upon induction of decidualization, the expression of mRNA for the major RA receptor sub-types (RAR-
, -ß and -
) was maintained while the relative amounts of CRABP-II mRNA progressively decreased with differentiation. With RA treatment, RAR- and RAR- mRNA concentrations were {small tilde}70 and 25% respectively of those in cells decidualized in the absence of RA. The effects of RA appear to be partially mediated by inhibition of cAMP action. RA suppressed intracellular cAMP concentrations induced by MPA and oestradiol to {small tilde}35% of those in cells without RA. Addition of 50 µM dibutyryl cAMP to stromal cells treated with MPA and oestradiol only partially reversed the suppression of decidualization and prolactin release by RA. In summary, we have demonstrated that in-vitro decidualization of human endometrial stromal cells induced by MPA and oestradiol treatment is suppressed by RA.
decidualization/fibronectin/IGFBP-1/prolactin/retinoic acid
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