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IUGR decreases cardiomyocyte endowment and alters cardiac metabolism in a sex and cause of IUGR specific manner

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  • Kimberley Jae Botting, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom; ajm267@cam.ac.uk.
  • ,
  • Xin Yee Loke
  • ,
  • Song Zhang
  • ,
  • Johnnie B Andersen
  • Jens Randel Nyengaard
  • Janna L Morrison, Early Origins of Adult Health Research Group, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia (K.J.B., C.M.M., H.F., J.L.M.).

Intrauterine growth restriction (IUGR) increases the risk of ischaemic heart disease in adulthood. Studies in rats suggest cardiac vulnerability is more pronounced in males and in offspring that were exposed to hypoxia in utero. Therefore, we aimed to test the hypotheses that 1) IUGR adolescent males, but not females, have fewer cardiomyocytes and altered expression of cardiometabolic genes compared to Controls and 2) IUGR due to hypoxia has a greater effect on these parameters compared to IUGR due to nutrient restriction. IUGR was induced in guinea pigs by Maternal Hypoxia (MH, 10% O2, n=9), or Maternal Nutrient Restriction (MNR, ~30% reduction in food intake, n=9) in the second half of pregnancy and compared to Control (n=11). At 120 days of age, post-mortem was performed, and the left ventricle perfusion fixed for stereological determination of cardiomyocyte number or snap frozen to determine the abundance of cardiometabolic genes and proteins by qRT-PCR and Western Blotting, respectively. MH reduced the number of cardiomyocytes in female (P<0.05), but not male or MNR, adolescent offspring. Furthermore, IUGR males had decreased expression of genes responsible for fatty acid activation in the sarcoplasm (FACS) and transport into the mitochondria (AMPKa2 and ACC; P<0.05) and females exposed to MH had increased activation/phosphorylation of AMPK (P<0.05). We postulate that the changes in cardiomyocyte endowment and cardiac gene expression observed in the present study are a direct result of in utero programming as offspring at this age did not suffer from obesity, hypertension or left ventricular hypertrophy.

Original languageEnglish
JournalA J P: Regulatory, Integrative and Comparative Physiology (Online)
Volume315
Issue1
Pages (from-to)48-67
Number of pages20
ISSN1522-1490
DOIs
Publication statusPublished - Jul 2018

    Research areas

  • Cardiac metabolism, Cardiomyocyte development, Intrauterine growth restriction

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