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The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-gamma and cell proliferation.
MedLine Citation:
PMID:  19525364     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Nutrient restriction (NR) during critical windows of pregnancy has differential effects on placento-fetal growth and development. Our study, therefore, investigated developmental and metabolic adaptations within the ovine placenta following NR at different critical windows during the first 110 days of gestation (term=147 days). Thus, the effects of NR on cell proliferation, glucocorticoid sensitivity, IGF1 and 2 receptor, peroxisome proliferator-activated receptor gamma (PPARG), and uncoupling protein (UCP)2 gene expression in the placenta were examined. Singleton bearing sheep (n=4-8 per group) were fed either 100% of their total metabolizable energy requirements throughout the study or 50% of this amount between 0-30, 31-65, 66-110, and 0-110 days gestation. A significant reduction in cell proliferation and increased gene expression for the glucocorticoid and IGF2 receptors, PPARG, and UCP2 were detected in placentae sampled from mothers who were nutrient restricted between days 66 and 110 of gestation, only, relative to controls. This window of gestation coincides with the maximum placental growth and the start of exponential growth of the fetus when there are substantially increased metabolic demands on the placenta compared with earlier in gestation. Consequently, increased glucocorticoid sensitivity and suppressed IGF2 action could contribute to a switch in the placenta from proliferation to differentiation, thereby improving its nutrient transfer capacity. Upregulation of PPARG and UCP2 would promote placental fatty acid metabolism thereby limiting glucose utilization. These compensatory placental responses may serve to maintain fetal growth but could result in adverse adaptations such as the early onset of the metabolic syndrome in later life.
Authors:
M Yiallourides; S P Sebert; V Wilson; D Sharkey; S M Rhind; M E Symonds; H Budge
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-12
Journal Detail:
Title:  Reproduction (Cambridge, England)     Volume:  138     ISSN:  1741-7899     ISO Abbreviation:  Reproduction     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100966036     Medline TA:  Reproduction     Country:  England    
Other Details:
Languages:  eng     Pagination:  601-8     Citation Subset:  IM    
Affiliation:
Early Life Nutrition Research Unit, Academic Child Health, School of Clinical Sciences, University Hospital, Nottingham NG72UH, UK.
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