DIMINISHED GROWTH OF ATRIOVENTRICULAR CUSHION TISSUE IN STAGE-24 RETINOIC-ACID-TREATED CHICKEN EMBRYOS

Stage 34 chicken hearts have shown a spectrum of looping disturbances, changed hemodynamics, and changed growth of both right ventricular my ocardium and atrioventricular cushion tissue after retinoic acid treat ment. To obtain more information about the onset of the malformations we studied stage 24, the stage between the previously studied stage 34 and the moment of treatment. Sixteen stage 24 chicken embryos were ex amined after treatment with 1 mu g all-trans retinoic acid at stage 15 and compared with 6 sham operated embryos. Morphological examination was supported by graphic reconstructions. Absolute volumes of atrial, atrioventricular, and ventricular myocardia were measured by a point c ounting method. The absolute volumes of the endocardial cushions were measured as well. Fifteen (15/16) retinoic acid-treated hearts did not show marked malformations as far as could be detected with our curren t macroscopic and microscopic techniques. One (1/16) retinoic acid-tre ated heart showed an abnormal tubular C-shape with a less bended inner curvature and with an abnormal horizontally oriented atrioventricular canal. The dorsal cushion tissue of this atrioventricular canal was d iscontinuous with the dorsal mesocardium and covered the malpositioned myocardial border between the atrium and the atrioventricular canal. The volume measurements did show a difference between retinoic acid tr eatment and sham operations. The retinoic acid-treated hearts showed a significant volume decrease of the atrioventricular cushions. No sign ificant differences were found in the volumes of the ventricular myoca rdium compared to the sham operated embryos. We hypothesize that, betw een stages 15 and 24, retinoic acid directly affects the myocardial wa ll and the cushion tissue formation. In the present material this has resulted in decreased atrioventricular cushion growth, in changed hemo dynamics, and in a severe looping disturbance of one embryo. We furthe r hypothesize that, between stages 24 and 34, the malformations with m inor looping disturbances will become apparent. Thus, development beyo nd stage 24 would result in the spectrum of looping disturbances as ha s been found at stage 34 These latter morphological malformations woul d lead to increasing hemodynamic changes, resulting in changes in grow th as a secondary effect. Dev. Dyn, 1998;213:50-58. (C) 1998 Wiley-Lis s, Inc.