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Stage of perinatal development regulates skeletal muscle mitochondrial biogenesis and myogenic regulatory factor genes with little impact of growth restriction or cross-fostering

Published online by Cambridge University Press:  10 November 2011

R. C. Laker
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
G. D. Wadley
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
G. K. McConell
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia Institute of Sport, Exercise and Active Living and the School of Biomedical and Health Sciences, Victoria University, Victoria, Australia
M. E. Wlodek*
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
*Author for correspondence: Prof M. E. Wlodek, Department of Physiology, The University of Melbourne, Parkville, Victoria 3010, Australia. (Email


Foetal growth restriction impairs skeletal muscle development and adult muscle mitochondrial biogenesis. We hypothesized that key genes involved in muscle development and mitochondrial biogenesis would be altered following uteroplacental insufficiency in rat pups, and improving postnatal nutrition by cross-fostering would ameliorate these deficits. Bilateral uterine vessel ligation (Restricted) or sham (Control) surgery was performed on day 18 of gestation. Males and females were investigated at day 20 of gestation (E20), 1 (PN1), 7 (PN7) and 35 (PN35) days postnatally. A separate cohort of Control and Restricted pups were cross-fostered onto a different Control or Restricted mother and examined at PN7. In both sexes, peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), cytochrome c oxidase subunits 3 and 4 (COX III and IV) and myogenic regulatory factor 4 expression increased from late gestation to postnatal life, whereas mitochondrial transcription factor A, myogenic differentiation 1 (MyoD), myogenin and insulin-like growth factor I (IGF-I) decreased. Foetal growth restriction increased MyoD mRNA in females at PN7, whereas in males IGF-I mRNA was higher at E20 and PN1. Cross-fostering Restricted pups onto a Control mother significantly increased COX III mRNA in males and COX IV mRNA in both sexes above controls with little effect on other genes. Developmental age appears to be a major factor regulating skeletal muscle mitochondrial and developmental genes, with growth restriction and cross-fostering having only subtle effects. It therefore appears that reductions in adult mitochondrial biogenesis markers likely develop after weaning.

Original Articles
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

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