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Retinoic acid administration is associated with changes in the extracellular matrix and cardiac mesenchyme within the
1Department of Anatomy, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
Abstract:
Retinoic acid has been associated with a number of cardiac defects, some of which seem to be related to changes in the endocardial cushions. Studies in mice and older chick embryos have suggested that these defects may be associated with a decrease in mesenchymal cell formation within the cushion. In a previous report we showed that retinoic acid lowered the number of mesenchymal cells in a culture bioassay of mesenchyme formation and that this response was due to retinoic acid modifying the production of particulate matrix from the myocardium. In this study, we have extended these observations to the embryo by implanting a retinoic acid coated bead into the embryo and examined the effect on cardiac mesenchyme formation and in the production of the particulate matrix. In all cases the addition of retinoic acid resulted in a decrease in the number of mesenchymal cells invading the endocardial cushions. In addition retinoic acid increased the production of hLAMP-1 and fibronectin but not transferrin, confirming our earlier report. Finally, we measured the volume of the cushion and calculated the cell density of both the inferior and superior cushions. The results suggest that the superior cushion is more sensitive to retinoic acid treatment than the inferior cushion. Collectively, these results support our earlier work that suggests that the mechanism of retinoic acid cardiac abnormalities involves a disruption in the production of particulate matrix from the myocardium and a subsequent decrease in cardiac mesenchyme cells that results in a malformed cardiac cushions.
Insights
Retinoic acid exposure during embryonic development reduces cardiac mesenchyme cells, leading to malformed heart cushions. This occurs due to altered myocardial matrix production, impacting heart development.
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Teratology
Background:
- Retinoic acid is linked to cardiac defects, potentially via endocardial cushion development.
- Previous studies suggest retinoic acid decreases mesenchymal cell formation in cardiac cushions.
Purpose of the Study:
- To investigate the in-embryo effects of retinoic acid on cardiac mesenchyme formation and matrix production.
- To confirm and extend previous in-vitro findings to a developing embryo model.
Main Methods:
- Implantation of retinoic acid-coated beads into chick embryos.
- Quantification of cardiac mesenchyme cells and analysis of specific matrix proteins (hLAMP-1, fibronectin, transferrin).
- Measurement of cardiac cushion volume and cell density.
Main Results:
- Retinoic acid significantly decreased mesenchymal cell invasion into endocardial cushions.
- Increased production of hLAMP-1 and fibronectin, but not transferrin, was observed.
- Superior cardiac cushions showed greater sensitivity to retinoic acid than inferior cushions.
Conclusions:
- Retinoic acid disrupts cardiac mesenchyme formation by altering myocardial matrix production.
- This leads to reduced mesenchymal cell numbers and malformed cardiac cushions.
- The findings support a mechanism for retinoic acid-induced cardiac abnormalities involving matrix disruption.
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