Aortic and ventricular dilation and myocardial reduction in gestation day 17 ICR mouse fetuses of diabetic mothers: Improvement of fetal heart development with complete Freund’s adjuvant and interferon gamma

Abstract

Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Non specific maternal immune stimulation has been described as protective against birth malformations. Using an ICR mouse model, late-gestation fetal heart and great vessel morphology were analyzed. Four groups of mice were used in these experiments: Non-hyperglycemic females as a control group, high hyperglycemic induced by streptozocin females as a positive control group and high hyperglycemic females injected either with complete Freund’s adjuvant (CFA) or interferon gamma (IF gamma). At day 17 of gestation, females were euthanized by cervical dislocation. One fetus was arbitrarily selected per litter to analyze the heart and great vessels. Fetuses were fixed in absolute ethanol for analysis. Fetal thoraxes were processed using routine histopathologic techniques and stained with hematoxylin and eosin. Digital images of sections were made using an Olympus microscope and camera, and images imported into computer software (Image J) to asses treatment-induced changes in cardiac developement. One way ANOVA was performed to compare the difference among groups (p < 0.05). Maternal hyperglycemia caused ventricular dilation, reduction of ventricular myocardial area and an increase in transversal aortic area. Immune-stimulation showed protection of the fetal heart from cavitary dilation in diabetic mothers that were treated with CFA. CFA and IF gamma protected the fetal heart against ascending thoracic aorta dilation. The mechanisms of immune protection remain unclear and represent an interesting line for future research.