Journal article
Maternal obesity induces fibrosis in fetal myocardium of sheep
American journal of physiology: endocrinology and metabolism, Vol.299(6), pp.E968-E975
12/2010
Handle:
https://hdl.handle.net/2376/100881
PMCID: PMC3006252
PMID: 20876759
Abstract
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.
Metrics
Details
- Title
- Maternal obesity induces fibrosis in fetal myocardium of sheep
- Creators
- Yan Huang - Developmental Biology Group and Center for the Study of Fetal Programming, Department of Animal Science andXu Yan - Developmental Biology Group and Center for the Study of Fetal Programming, Department of Animal Science andJun X Zhao - Developmental Biology Group and Center for the Study of Fetal Programming, Department of Animal Science andMei J Zhu - Developmental Biology Group and Center for the Study of Fetal Programming, Department of Animal Science andRichard J McCormick - Developmental Biology Group and Center for the Study of Fetal Programming, Department of Animal Science andStephen P Ford - Developmental Biology Group and Center for the Study of Fetal Programming, Department of Animal Science andPeter W Nathanielsz - Center for Pregnancy and Newborn Research, University of Texas, Health Sciences Center, San Antonio, TexasJun Ren - Center for Cardiovascular Research and Alternative Medicine, School of Pharmacy, University of Wyoming, Laramie, Wyoming; andMin Du - Developmental Biology Group and Center for the Study of Fetal Programming, Department of Animal Science and
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.299(6), pp.E968-E975
- Academic Unit
- Department of Animal Sciences
- Publisher
- American Physiological Society; Bethesda, MD
- Grant note
- P20-RR-016474; 1R03-HD-057506 / National Institutes of Health
- Identifiers
- 99900546631901842
- Language
- English
- Resource Type
- Journal article