Document Detail


Maternal obesity induces fibrosis in fetal myocardium of sheep.
MedLine Citation:
PMID:  20876759     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring 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.
Authors:
Yan Huang; Xu Yan; Jun X Zhao; Mei J Zhu; Richard J McCormick; Stephen P Ford; Peter W Nathanielsz; Jun Ren; Min Du
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-28
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  299     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2010-12-28     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E968-75     Citation Subset:  IM    
Affiliation:
Dept. of Animal Science, Univ. of Wyoming, Laramie, WY 82071, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Female
Fibrosis
Heart / embryology
Maternal Nutritional Physiological Phenomena / physiology*
Matrix Metalloproteinase 9 / metabolism
Myocardium / metabolism,  pathology*
Obesity / metabolism,  pathology*
Phosphorylation
Pregnancy
Reverse Transcriptase Polymerase Chain Reaction
Sheep
Signal Transduction
Tissue Inhibitor of Metalloproteinase-3 / metabolism
Transforming Growth Factor beta / metabolism
p38 Mitogen-Activated Protein Kinases / metabolism
Grant Support
ID/Acronym/Agency:
1R03-HD-057506/HD/NICHD NIH HHS; P20-RR-016474/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Tissue Inhibitor of Metalloproteinase-3; 0/Transforming Growth Factor beta; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

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