title: Heart changes in 17-day-old fetuses of diabetic ICR (Institute of Cancer Research) mothers: improvement with maternal immune stimulation.
abstract: Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Non-specific maternal immune stimulation with Freund's complete adjuvant (FCA) or interferon gamma (IFNgamma) has been associated with protection against birth malformations. Using a diabetic mouse model, late-gestation fetal heart and great vessel morphology were analyzed. Four groups of mice were used: non-diabetic females as a control group, hyperglycemic females induced by streptozotocin as a diabetic group, and diabetic females injected either with FCA or IFNgamma. At day 17 of gestation, females were euthanized and one fetus was arbitrarily selected per litter for fixation and sectioning. Treatment-induced changes in cardiac development were assessed from digital images of serial sections taken at standardized levels in the thorax. One-way parametric and non-parametric ANOVA and ordinal logistic regression were performed to compare the difference among groups (P<0.05). Maternal hyperglycemia altered morphology of the late-gestation fetal mouse heart by causing ventricular chamber dilation, sectional myocardial reduction, and an increase in transversal aortic area. FCA protected the fetal heart from cavitary dilation in diabetic mothers. FCA and IFNgamma protected the fetal heart against reduction of myocardial area, and ascending thoracic aorta dilation. Consequences of late gestation heart chamber dilation and myocardial reduction are not yet known. Maternal immune stimulation partially protected against these developmental defects by mechanisms that remain unclear.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. jcgutier@vt.edu
authors.forename: Juan
authors.initials: J
authors.lastname: Claudio Gutierrez
authors.forename: Mary Renee
authors.initials: MR
authors.lastname: Prater
authors.forename: Theresa C
authors.initials: TC
authors.lastname: Hrubec
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: Smith
authors.forename: Larry E
authors.initials: LE
authors.lastname: Freeman
authors.forename: Steven D
authors.initials: SD
authors.lastname: Holladay
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D006330:Heart Defects, Congenital / Q000209:etiology* / Q000276:immunology* / Q000517:prevention & control; D006352:Heart Ventricles / Q000196:embryology / Q000473:pathology*; D006943:Hyperglycemia / Q000150:complications; D007107:Immune System; D007371:Interferon-gamma / Q000494:pharmacology; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011254:Pregnancy in Diabetics
chemical_list: D007371:Interferon-gamma; D005620:Freund's Adjuvant