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Oocyte developmental failure in response to elevated non-esterified fatty acid concentrations: mechanistic insights.
MedLine Citation:
PMID:  23108110     Owner:  NLM     Status:  Publisher    
Elevated plasma non-esterified fatty acid (NEFA) concentrations are associated with negative energy balance (NEB) and metabolic disorders such as obesity and type 2 diabetes. Increased plasma NEFA induce changes in the micro-environment of the ovarian follicle, which can compromise oocyte competence. Exposing oocytes to elevated NEFA concentrations during maturation affects the gene expression and phenotype of the subsequent embryo, notably prompting a disrupted oxidative metabolism. We hypothesized that these changes in the embryo are a consequence of modified energy metabolism in the oocyte. To investigate this, bovine cumulus oocyte complexes were matured under elevated NEFA conditions, and energy metabolism-related gene expression, mitochondrial function and ultrastructure evaluated. It was found that expression of genes related to REDOX maintenance was modified in NEFA-exposed oocytes, cumulus cells and resultant blastocysts. Moreover, the expression of genes related to fatty acid synthesis in embryos that developed from NEFA-exposed oocytes, was up-regulated. From a functional perspective, inhibition of fatty acid β-oxidation in maturing oocytes exposed to elevated NEFA concentrations restored developmental competence. There were no clear differences in mitochondrial morphology or oxygen consumption between treatments although there was a trend for a higher mitochondrial membrane potential in zygotes derived from NEFA-exposed oocytes. These data show that the degree of mitochondrial fatty acid β-oxidation has a decisive impact on the development of NEFA-exposed oocytes. Furthermore, the gene expression data suggest that the resulting embryos adapt through altered metabolic strategies, which might explain the aberrant energy metabolism previously observed in these embryos originating from NEFA exposed maturing oocytes.
Veerle Van Hoeck; Jo Leo Leroy; María Arias-Álvarez; Dimitrios Rizos; Alfonso Gutierrez-Adan; Kathy Schnorbusch; Peter E J Bols; Henry J Leese; Roger G S Sturmey
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-29
Journal Detail:
Title:  Reproduction (Cambridge, England)     Volume:  -     ISSN:  1741-7899     ISO Abbreviation:  Reproduction     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100966036     Medline TA:  Reproduction     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
V Van Hoeck, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
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