title: Retinoic acid-induced ventricular non-compacted cardiomyopathy in mice.
abstract: BACKGROUND
  Precise tissue concentration of retinoic acid (RA) is indispensable for proper interaction of second heart field cells with cardiac neural crest cells and induction of signalling pathways important for normal myocardial growth.
  
  
  OBJECTIVE
  Since RA deficiency during embryogenesis induces noncompaction, we hypothesised that excess RA at the stage of heart tube elongation may cause thinning of the myocardial wall which leads to noncompaction.
  
  
  METHODS
  RA was administered at 70 mg/kg b.w. on 8.5 days post coitus (dpc) to pregnant mice to elicit cardiac malformations in foetuses. We studied noncompaction development in RA-treated mouse offspring. The cardiac noncompaction was evaluated in different stages of heart development as the quotient of the distance between the epicardial surface and trabecular tips(represented by a) and the distance between the epicardial surface and trabecular recesses (represented by b) in RA-treated hearts compared to control non-treated.
  
  
  RESULTS
  We demonstrated that apart from outflow tract defects such as double outlet right ventricle, transposition of the great arteries and tetralogy of Fallot in foetuses in mouse offspring, noncompaction occurs in about 42% of cases. At the stage of 13 dpc and later in development the ratio a/b was higher in RA-treated hearts exhibiting noncompaction compared to the control hearts. This cardiomyopathy was more evident in the right ventricle than in the left ventricle.
  
  
  CONCLUSIONS
  Noncompaction caused by RA overdose can be elicited in part of the mouse offspring by administering RA at the stage of cardiac tube elongation.
authors.affiliation: Department of Pathomorphology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kołodzińska
authors.forename: Anna
authors.initials: A
authors.lastname: Heleniak
authors.forename: Anna
authors.initials: A
authors.lastname: Ratajska
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D062787:Drug Overdose / Q000150:complications; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000196:embryology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009206:Myocardium / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D014057:Tomography, X-Ray Computed; D014212:Tretinoin / Q000633:toxicity*
chemical_list: D014212:Tretinoin