title: Retinoic acid administration is associated with changes in the extracellular matrix and cardiac mesenchyme within the endocardial cushion.
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.
authors.affiliation: Department of Anatomy, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.forename: A R
authors.initials: AR
authors.lastname: Sinning
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D002452:Cell Count; D002642:Chick Embryo; D004694:Endocardial Cushion Defects / Q000139:chemically induced* / Q000196:embryology; D004699:Endocardium / Q000187:drug effects / Q000196:embryology; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000196:embryology*; D008648:Mesoderm / Q000187:drug effects; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D014168:Transferrin / Q000032:analysis / Q000378:metabolism; D014212:Tretinoin / Q000633:toxicity*
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; C105075:HLAMP1 protein, Gallus gallus; D014168:Transferrin; D014212:Tretinoin