IUGR impairs cardiomyocyte growth and maturation in fetal sheep

Sonnet Jonker, Daniel Kamna, Dan LoTurco, Jenai Kailey, Laura D. Brown

    Research output: Contribution to journalArticle

    Abstract

    Placental insufficiency causes intrauterine growth restriction (IUGR), a common complication of pregnancy. In skeletal muscle, IUGR reduces fetal myofibril size, reduces myoblast proliferation and reduces expression of genes in cell cycle regulation clusters. The myocardium is striated like skeletal muscle, and IUGR also reduces cell cycle activity and maturation in cardiomyocytes, despite cardiac output preferentially directed to the coronary circulation. We hypothesized that cardiomyocyte growth restriction would be accompanied by similar changes in cell cycle regulation genes and would reduce cardiomyocyte cell cycle activity, number, maturity and size. Pregnant ewes were housed in elevated ambient temperatures from ~40 to ~115 days of gestation (dGA) to produce placental insufficiency and IUGR; fetal hearts were studied at ~134 dGA. Hearts were biopsied for mRNA analysis and then dissociated into individual myocytes (Control n = 8; IUGR n = 15) or dissected (Control n = 9; IUGR n = 13). IUGR fetuses had low circulating insulin and insulin-like growth factor 1 (IGF1) and high circulating cortisol. Bodies and hearts of IUGR fetuses were lighter than those of Controls. Cardiomyocytes of IUGR fetuses were smaller, less mature, less active in the cell cycle and less numerous than in Controls. Further, there was a pattern of downregulation of cell cycle genes in IUGR ventricles. IUGR growth profiles in heart and skeletal muscle suggest similar regulation despite differences in blood and nutrient delivery prioritization. IGF1 signaling is suggested as a mechanism regulating altered growth in IUGR striated muscle and a potential therapeutic candidate.

    Original languageEnglish (US)
    Pages (from-to)253-265
    Number of pages13
    JournalJournal of Endocrinology
    Volume239
    Issue number2
    DOIs
    StatePublished - Nov 1 2018

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    Cardiac Myocytes
    Sheep
    Growth
    cdc Genes
    Placental Insufficiency
    Cell Cycle
    Skeletal Muscle
    Fetus
    Somatomedins
    Myocardium
    Fetal Heart
    Pregnancy
    Coronary Circulation
    Striated Muscle
    Pregnancy Complications
    Myofibrils
    Myoblasts
    Cardiac Output
    Muscle Cells
    Hydrocortisone

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

    Cite this

    IUGR impairs cardiomyocyte growth and maturation in fetal sheep. / Jonker, Sonnet; Kamna, Daniel; LoTurco, Dan; Kailey, Jenai; Brown, Laura D.

    In: Journal of Endocrinology, Vol. 239, No. 2, 01.11.2018, p. 253-265.

    Research output: Contribution to journalArticle

    Jonker, S, Kamna, D, LoTurco, D, Kailey, J & Brown, LD 2018, 'IUGR impairs cardiomyocyte growth and maturation in fetal sheep', Journal of Endocrinology, vol. 239, no. 2, pp. 253-265. https://doi.org/10.1530/JOE-18-0382
    Jonker, Sonnet ; Kamna, Daniel ; LoTurco, Dan ; Kailey, Jenai ; Brown, Laura D. / IUGR impairs cardiomyocyte growth and maturation in fetal sheep. In: Journal of Endocrinology. 2018 ; Vol. 239, No. 2. pp. 253-265.
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