title: Avian model for 13-cis-retinoic acid embryopathy: morphological characterization of ventricular septal defects.
abstract: In developing an avian model for 13-cis-retinoic acid (13cisRA) embryopathy, we found 13cisRA induced cardiovascular defects, especially Type I ventricular septal defects (VSDs) (Hart et al.: Teratology 41:463-472, '90). As the first step of investigating possible mechanisms, we have examined the light microscopic morphology of RA-induced cardiovascular defects in chick embryos. Fertilized eggs were injected via yolk sac with 150 micrograms 13cisRA in dimethylsulfoxide (DMSO), DMSO or mock injection on embryonic day 5 (E5). On E6, E7, or E8, surviving embryos were sacrificed and fixed in 10% formalin. Thoracic blocks were exised, embedded in paraffin and serially sectioned through the heart, base to apex. Slides were stained, screened for tissue orientation, then coded and evaluated without knowledge of treatment group. Examination of serial sections permitted qualitative evaluation of conotruncal ridge volume, mesenchymal organization, necrosis and extent of fusion. Extent of fusion was the only parameter influenced by 13cisRA treatment. On E6, ridge fusion was incomplete in all groups at comparable levels. On E7, ridge fusion in 13cisRA-treated embryos had not progressed as far proximally as in controls. By E8, there was a significant difference in the extent of fusion between 13cisRA-treated and non-RA-treated groups. We conclude 13cisRA-induced VSDs resulted from defective conotruncal ridge fusion and that the fusion defects did not result from decreased tissue volume, altered mesenchymal organization or increased necrosis.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322.
authors.forename: R C
authors.initials: RC
authors.lastname: Hart
authors.forename: K J
authors.initials: KJ
authors.lastname: Winn
authors.forename: E R
authors.initials: ER
authors.lastname: Unger
mesh_terms: D000818:Animals; D002642:Chick Embryo; D004195:Disease Models, Animal; D005865:Gestational Age; D006343:Heart Septal Defects / Q000139:chemically induced / Q000196:embryology*; D015474:Isotretinoin / Q000633:toxicity*
chemical_list: D015474:Isotretinoin