title: Maternal hyperglycemia leads to fetal cardiac hyperplasia and dysfunction in a rat model.
abstract: Accelerated fetal myocardial growth with altered cardiac function is a well-documented complication of human diabetic pregnancy, but its pathophysiology is still largely unknown. Our aim was to explore the mechanisms of fetal cardiac remodeling and cardiovascular hemodynamics in a rat model of maternal pregestational streptozotocin-induced hyperglycemia. The hyperglycemic group comprised 107 fetuses (10 dams) and the control group 219 fetuses (20 dams). Fetal cardiac function was assessed serially by Doppler ultrasonography. Fetal cardiac to thoracic area ratio, newborn heart weight, myocardial cell proliferative and apoptotic activities, and cardiac gene expression patterns were determined. Maternal hyperglycemia was associated with increased cardiac size, proliferative, apoptotic and mitotic activities, upregulation of genes encoding A- and B-type natriuretic peptides, myosin heavy chain types 2 and 3, uncoupling proteins 2 and 3, and the angiogenetic tumor necrosis factor receptor superfamily member 12A. The genes encoding Kv channel-interacting protein 2, a regulator of electrical cardiac phenotype, and the insulin-regulated glucose transporter 4 were downregulated. The heart rate was lower in fetuses of hyperglycemic dams. At 13-14 gestational days, 98% of fetuses of hyperglycemic dams had holosystolic atrioventricular valve regurgitation and decreased outflow mean velocity, indicating diminished cardiac output. Maternal hyperglycemia may lead to accelerated fetal myocardial growth by cardiomyocyte hyperplasia. In fetuses of hyperglycemic dams, expression of key genes that control and regulate cardiomyocyte electrophysiological properties, contractility, and metabolism are altered and may lead to major functional and clinical implications on the fetal heart.
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland;
authors.forename: Lara
authors.initials: L
authors.lastname: Lehtoranta
authors.forename: Olli
authors.initials: O
authors.lastname: Vuolteenaho
authors.forename: V Jukka
authors.initials: VJ
authors.lastname: Laine
authors.forename: Anna
authors.initials: A
authors.lastname: Koskinen
authors.forename: Hanna
authors.initials: H
authors.lastname: Soukka
authors.forename: Ville
authors.initials: V
authors.lastname: Kytö
authors.forename: Jorma
authors.initials: J
authors.lastname: Määttä
authors.forename: Mervi
authors.initials: M
authors.lastname: Haapsamo
authors.forename: Eeva
authors.initials: E
authors.lastname: Ekholm
authors.forename: Juha
authors.initials: J
authors.lastname: Räsänen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D005318:Fetal Heart / Q000000981:diagnostic imaging / Q000473:pathology*; D006339:Heart Rate / Q000502:physiology; D006943:Hyperglycemia / Q000097:blood* / Q000473:pathology*; D006965:Hyperplasia; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D018608:Ultrasonography, Doppler
chemical_list: D012313:RNA
keywords: dysfunction; fetal heart; hyperglycemia; hyperplasia; rats