Anemic hypoxemia reduces myoblast proliferation and muscle growth in lategestation fetal sheep

Paul J. Rozance, Stephanie R. Wesolowski, Sonnet S. Jonker, Laura D. Brown

    Research output: Contribution to journalArticlepeer-review

    2 Scopus citations


    Fetal skeletal muscle growth requires myoblast proliferation, differentiation, and fusion into myofibers in addition to protein accretion for fiber hypertrophy. Oxygen is an important regulator of this process. Therefore, we hypothesized that fetal anemic hypoxemia would inhibit skeletal muscle growth. Studies were performed in late-gestation fetal sheep that were bled to anemic and therefore hypoxemic conditions beginning at ~125 days of gestation (term = 148 days) for 9 ± 0 days (n = 19) and compared with control fetuses (n = 16). A metabolic study was performed on gestational day ~134 to measure fetal protein kinetic rates. Myoblast proliferation and myofiber area were determined in biceps femoris (BF), tibialis anterior (TA), and flexor digitorum superficialis (FDS) muscles. mRNA expression of muscle regulatory factors was determined in BF. Fetal arterial hematocrit and oxygen content were 28% and 52% lower, respectively, in anemic fetuses. Fetal weight and whole body protein synthesis, breakdown, and accretion rates were not different between groups. Hindlimb length, however, was 7% shorter in anemic fetuses. TA and FDS muscles weighed less, and FDS myofiber area was smaller in anemic fetuses compared with controls. The percentage of Pax7+ myoblasts that expressed Ki67 was lower in BF and tended to be lower in FDS from anemic fetuses indicating reduced myoblast proliferation. There was less MYOD and MYF6 mRNA expression in anemic versus control BF consistent with reduced myoblast differentiation. These results indicate that fetal anemic hypoxemia reduced muscle growth. We speculate that fetal muscle growth may be improved by strategies that increase oxygen availability.

    Original languageEnglish (US)
    Pages (from-to)R352-R363
    JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
    Issue number3
    StatePublished - Aug 25 2021


    • Fetal growth
    • Fetal hypoxemia
    • Fetal protein accretion
    • Myogenesis
    • Skeletal muscle

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)


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