Maternal obesity induces fibrosis in fetal myocardium of sheep

Yan Huang, Xu Yan, Jun X. Zhao, Mei J. Zhu, Richard J. McCormick, Stephen P. Ford, Peter W. Nathanielsz, Jun Ren, Min Du

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Maternal obesity (MO) has harmful effects on both fetal development and subsequent off-spring health. The impact of MO on fetal myocardium development has received little attention. Fibrogenesis is regulated by the transforming growth factor-β (TGF-β)/p38 signaling pathway. Using the well-established model of MO in pregnant sheep, we evaluated the effect of MO on TGF-β/p38 and collagen accumulation in fetal myocardium. Nonpregnant ewes were assigned to a control diet [Con, fed 100% of National Research Council (NRC) nutrient recommendations] or obesogenic diet (OB, fed 150% of NRC recommendations) from 60 days before conception. Fetal ventricular muscle was sampled at 75 and 135 days of gestation (dG). At 75 dG, the expression of precursor TGF-β was 39.9 ± 9.9% higher (P < 0.05) in OB than Con fetal myocardium, consistent with the higher content of phosphorylated Smad3 in OB myocardium. The phosphorylation of p38 tended to be higher in OB myocardium (P = 0.08). In addition, enhanced Smad complexes were bound to Smad-binding elements in 75 dG OB fetal myocardium measured by DNA mobility shift assay (130.2 ± 26.0% higher, P < 0.05). Similar elevation of TGF-β signaling was observed in OB fetal myocardium at 135 dG. Total collagen concentration in OB was greater than Con fetal myocardium (2.42 ± 0.16 vs. 1.87 ± 0.04%, P < 0.05). Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 were higher in the Con group compared with OB sheep (43.86 ± 16.01 and 37.23 ± 7.97% respectively, P < 0.05). In summary, MO results in greater fetal heart connective tissue accumulation associated with an upregulated TGF-β/p38 signaling pathway at late gestation; such changes would be expected to negatively impact offspring heart function.

Original languageEnglish (US)
Pages (from-to)E968-E975
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume299
Issue number6
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • Collagen
  • Fetus
  • Fibrogenesis
  • Maternal obesity
  • Myocardium
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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  • Cite this

    Huang, Y., Yan, X., Zhao, J. X., Zhu, M. J., McCormick, R. J., Ford, S. P., Nathanielsz, P. W., Ren, J., & Du, M. (2010). Maternal obesity induces fibrosis in fetal myocardium of sheep. American Journal of Physiology - Endocrinology and Metabolism, 299(6), E968-E975. https://doi.org/10.1152/ajpendo.00434.2010