Myoblast replication is reduced in the IUGR fetus despite maintained proliferative capacity in vitro

Research output: Contribution to journalArticle

Authors

  • Susan M. Soto
  • Amy C. Blake
  • Stephanie R. Wesolowski
  • Paul J. Rozance
  • Kristen B. Barthel
  • Bifeng Gao
  • Byron Hetrick
  • Carrie E. McCurdy
  • Natalia G. Garza
  • William W. Hay
  • Leslie A. Leinwand
  • Jacob E. Friedman
  • Laura D. Brown

External Institution(s)

  • University of Colorado Denver
  • University of Oregon

Details

Original languageEnglish (US)
Pages (from-to)475-491
Number of pages17
JournalJournal of Endocrinology
Volume232
Issue number3
StatusPublished - Jan 1 2017
Peer-reviewedYes

Abstract

Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass and insulin resistance, suggesting muscle growth may be restricted by molecular events that occur during fetal development. To explore the basis of restricted fetal muscle growth, we used a sheep model of progressive placental insufficiency-induced IUGR to assess myoblast proliferation within intact skeletal muscle in vivo and isolated myoblasts stimulated with insulin in vitro. Gastrocnemius and soleus muscle weights were reduced by 25% in IUGR fetuses compared to those in controls (CON). The ratio of PAX7+ nuclei (a marker of myoblasts) to total nuclei was maintained in IUGR muscle compared to CON, but the fraction of PAX7+ myoblasts that also expressed Ki-67 (a marker of cellular proliferation) was reduced by 23%. Despite reduced proliferation in vivo, fetal myoblasts isolated from IUGR biceps femoris and cultured in enriched media in vitro responded robustly to insulin in a dose- and time-dependent manner to increase proliferation. Similarly, insulin stimulation of IUGR myoblasts upregulated key cell cycle genes and DNA replication. There were no differences in the expression of myogenic regulatory transcription factors that drive commitment to muscle differentiation between CON and IUGR groups. These results demonstrate that the molecular machinery necessary for transcriptional control of proliferation remains intact in IUGR fetal myoblasts, indicating that in vivo factors such as reduced insulin and IGF1, hypoxia and/or elevated counter-regulatory hormones may be inhibiting muscle growth in IUGR fetuses.

    Research areas

  • Fetal programming, Muscle growth, Myogenesis, Skeletal muscle

Citation formats

APA

Soto, S. M., Blake, A. C., Wesolowski, S. R., Rozance, P. J., Barthel, K. B., Gao, B., ... Brown, L. D. (2017). Myoblast replication is reduced in the IUGR fetus despite maintained proliferative capacity in vitro. Journal of Endocrinology, 232(3), 475-491. https://doi.org/10.1530/JOE-16-0123

Harvard

Soto, SM, Blake, AC, Wesolowski, SR, Rozance, PJ, Barthel, KB, Gao, B, Hetrick, B, McCurdy, CE, Garza, NG, Hay, WW, Leinwand, LA, Friedman, JE & Brown, LD 2017, 'Myoblast replication is reduced in the IUGR fetus despite maintained proliferative capacity in vitro', Journal of Endocrinology, vol. 232, no. 3, pp. 475-491. https://doi.org/10.1530/JOE-16-0123