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Retinoic acid suppresses in-vitro decidualization of human endometrial stromal cells
A K Brar1, C A Kessler, A J Meyer
1Division of Endocrinology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Abstract:
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-II (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 approximately 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-alpha, -beta and -gamma) was maintained while the relative amounts of CRABP-II mRNA progressively decreased with differentiation. With RA treatment, RAR-alpha and RAR-gamma mRNA concentrations were approximately 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 approximately 35% of those in cells without RA. Addition of 50 microM 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.
Insights
All-trans retinoic acid (RA) suppresses human endometrial stromal cell decidualization. RA inhibits key markers like prolactin and IGFBP-1, impacting uterine receptivity for implantation.
Area of Science:
- Reproductive Biology
- Endocrinology
- Cellular Differentiation
Background:
- Human endometrial stromal cells undergo decidualization for successful pregnancy.
- All-trans retinoic acid (RA) influences cell differentiation and gene expression.
- Retinoic acid receptors (RARs) and CRABP-II are present in endometrial stromal cells.
Purpose of the Study:
- To investigate the effect of RA on human endometrial stromal cell decidualization.
- To determine if RA regulates key markers of decidualization, such as prolactin and IGFBP-1.
- To explore the role of RA receptors and cAMP signaling in this process.
Main Methods:
- Cultured human endometrial stromal cells were treated with medroxyprogesterone acetate (MPA) and oestradiol to induce decidualization.
- RA was added to assess its impact on decidualization markers (prolactin, IGFBP-1, fibronectin).
- Expression of RAR subtypes and CRABP-II mRNA was analyzed; intracellular cAMP levels were measured.
Main Results:
- RA significantly suppressed the production of prolactin and IGFBP-1.
- RA inhibited the formation of differentiated cells and increased fibronectin mRNA levels.
- RA reduced RAR-alpha and RAR-gamma mRNA expression and suppressed MPA/oestradiol-induced intracellular cAMP concentrations.
Conclusions:
- All-trans retinoic acid (RA) suppresses in-vitro decidualization of human endometrial stromal cells.
- RA interferes with key decidualization markers and alters RA receptor expression.
- The suppressive effects of RA may be partly mediated through inhibition of cAMP signaling.