ANOMALOUS LOOPING, ATRIOVENTRICULAR CUSHION DYSPLASIA, AND UNILATERALVENTRICULAR HYPOPLASIA IN THE MOUSE EMBRYOS WITH RIGHT ISOMERISM INDUCED BY RETINOIC ACID

Background: Visceroatrial heterotaxy syndrome is characterized by abno rmality of visceral laterality and complex cardiovascular anomalies us ually involving both the outflow and inflow tract, Morishima et al. (1 995) showed that mouse embryos treated with all-trans retinoic acid at embryonic day 6.5 (primitive streak stage) induces this syndrome, Met hods: To investigate the morphogenetic process of visceroatrial hetero taxy syndrome, we examined retinoic acid-treated mouse embryos at embr yonic days 9-15 using scanning electron microscopy. Results: The sinoa trial connection was first distinguished for the determination of situ s as early as at embryonic day 10.5, Normal visceroatrial situs was fo und in 57% of all treated embryos, and the rest had abnormal situs, in which right isomerism was found in 81%, In the right-isomeric mouse, the cardiac morphology was characterized by abnormal looping together with dysplasia of the inflow and outflow tract cushion; that is, the p rimitive right ventricle was usually deviated cranially to various deg rees, the atrioventricular cushion appeared trilobed in a half of them , and unilateral ventricular hypoplasia was noted in about one-third o f them after embryonic day 14.5, Conclusions: An anomalous relation be tween the atrioventricular cushions and the interventricular septum ap peared to have caused a restrictive inflow to the unilateral ventricle , leading to ventricular chamber hypoplasia on the ipsilateral side. T hus, we clarified that retinoic-acid treatment at the primitive streak stage disturbed cardiac looping and formation of atrioventricular cus hion development, which secondarily influenced ventricular chamber dev elopment. (C) 1998 Wiley-Liss, Inc.