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: Lara Lehtoranta, Olli Vuolteenaho, V Jukka Laine, Anna Koskinen, Hanna Soukka, Ville Kytö, Jorma Määttä, Mervi Haapsamo, Eeva Ekholm, Juha Räsänen
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 305 Issue 5 Pg. E611-9 (Sep 01 2013) ISSN: 1522-1555 [Electronic] United States
• PMID: 23839525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA

Topics

• Animals
• Apoptosis (physiology)
• Female
• Fetal Heart (diagnostic imaging, pathology)
• Heart Rate (physiology)
• Hyperglycemia (blood, pathology)
• Hyperplasia
• Organ Size (physiology)
• Pregnancy
• Pregnancy in Diabetics (blood, diagnostic imaging, pathology)
• RNA (chemistry, genetics)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Tomography, X-Ray Computed
• Ultrasonography, Doppler