Development and histo-functional cardiac abnormalities in murine fetuses after perigestational alcohol consumption up to early organogenesis

VENTUREIRA, MR; SOBARZO C; CHALIMONIUK G; BARBEITO C; CEBRAL E

CABA

Congreso; Reunión conjunta de Sociedades de Biociencias; 2017

SAIC

DEVELOPMENT ANDHISTO-FUNCTIONAL CARDIAC ABNORMALITIES IN MURINE FETUSES AFTER PERIGESTATIONAL ALCOHOL CONSUMPTION UP TO EARLY ORGANOGENESISVentureira  M1,Sobarzo C2, Chalimoniuk G1, Barbeito C3, Cebral E1. 1Laboratorio de Reproducción y FisiologíaMaterno-Embrionaria, Instituto de Biodiversidad y Biología Experimental yAplicada (IBBEA-UBA/CONICET), Facultad de Ciencias Exactas y Naturales (FCEN),Universidad de Buenos Aires. 2 INBIOMED-UBA/CONICET,Facultad de Medicina-UBA.3Laboratorio de Histología y Embriología Descriptiva, Experimental yComparada, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata (UNLP). Maternal alcoholconsumption leads to congenital diseases and organ malformation, in which the developingheart is one of main target for teratogenic maternal alcohol effects. The aimof this study was to assess if perigestational alcohol intake up to day 10 ofgestation (D10) alters the heart rate and ventricular and atrial myocardial andendocardial arrangement, and modifies the proliferation and apoptotic indexes,in fetal heart at day 13 of gestation (D13). Ethanol 10% in drinking water was administered to murine CF-1 femalesfor 15 days before and up to D10, and gestation continued with water until D13 (treatedfemales (TF)). Control females (CF) were administered with drinking waterwithout ethanol. Both in morphologically abnormal and normal fetuses of TF, the hearts presented thinner trabeculation anddiscontinuous endocardium (Hematoxylin-eosin), and the ventricular and atrialmyocardial wall thickness were reduced (p<0.001) compared to CF-fetuses. At20-40 minutes of uterus extraction, the heart rate of TF-fetuses was reducedrespect to CF-heart rate (p<0.01). In TF-fetuses, cardiomyocyticmyofilaments and mitochondrias were disorganized, while high cellular debriswas observed in the ventricular lumen near the endocardium (Transmissionelectron microscopy). Hearts of TF-fetuses had a reduced myocardialproliferation index (Ki67 immunohistochemistry, p<0.05) and increasedapoptosis, measured by active Caspase-3-positive cells/myocardial area(p<0.05) compared to CF. In conclusion, perigestational alcohol consumptionup to early organogenesis induced atrial and ventricular abnormal development,decreased growth, altered functionality and histo-morphology in fetuses at D13of gestation. Despite the cessation of alcohol intakeat D10, probably the fetal cardiac defects, induced during alcohol exposure inearly embryo organogenesis, continue at term and yield to the typicalcongenital cardiopathy observed in the Fetal Alcohol Spectrum