Maternal hyperglycemia leads to fetal cardiac hyperplasia and dysfunction in a rat model

Lara Lehtoranta, Olli Vuolteenaho, V. Jukka Laine, Anna Koskinen, Hanna Soukka, Ville Kytö, Jorma Määttä, Mervi Haapsamo, Eeva Ekholm, Juha Rasanen

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume305
Issue number5
DOIs
StatePublished - 2013
Externally publishedYes

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Hyperglycemia
Hyperplasia
Fetus
Mothers
Fetal Development
Cardiac Myocytes
Kv Channel-Interacting Proteins
Gene Expression
Fetal Heart
Doppler Ultrasonography
Facilitative Glucose Transport Proteins
Myosin Heavy Chains
Brain Natriuretic Peptide
Diabetes Complications
Streptozocin
Cardiac Output
Genes
Up-Regulation
Thorax
Down-Regulation

Keywords

  • Dysfunction
  • Fetal heart
  • Hyperglycemia
  • Hyperplasia
  • Rats

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Maternal hyperglycemia leads to fetal cardiac hyperplasia and dysfunction in a rat model. / Lehtoranta, Lara; Vuolteenaho, Olli; Jukka Laine, V.; Koskinen, Anna; Soukka, Hanna; Kytö, Ville; Määttä, Jorma; Haapsamo, Mervi; Ekholm, Eeva; Rasanen, Juha.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 305, No. 5, 2013.

Research output: Contribution to journalArticle

Lehtoranta, L, Vuolteenaho, O, Jukka Laine, V, Koskinen, A, Soukka, H, Kytö, V, Määttä, J, Haapsamo, M, Ekholm, E & Rasanen, J 2013, 'Maternal hyperglycemia leads to fetal cardiac hyperplasia and dysfunction in a rat model', American Journal of Physiology - Endocrinology and Metabolism, vol. 305, no. 5. https://doi.org/10.1152/ajpendo.00043.2013
Lehtoranta, Lara ; Vuolteenaho, Olli ; Jukka Laine, V. ; Koskinen, Anna ; Soukka, Hanna ; Kytö, Ville ; Määttä, Jorma ; Haapsamo, Mervi ; Ekholm, Eeva ; Rasanen, Juha. / Maternal hyperglycemia leads to fetal cardiac hyperplasia and dysfunction in a rat model. In: American Journal of Physiology - Endocrinology and Metabolism. 2013 ; Vol. 305, No. 5.
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