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Oocyte developmental failure in response to elevated nonesterified fatty acid concentrations: mechanistic insights

Van Hoeck, V.; Leroy, J. L. M. R.; Arias Alvarez, M.; Rizos, D.; Gutierrez-Adan, A.; Schnorbusch, K.; Bols, P. E. J.; Leese, H. J.; Sturmey, R. G.


V. Van Hoeck

J. L. M. R. Leroy

M. Arias Alvarez

D. Rizos

A. Gutierrez-Adan

K. Schnorbusch

P. E. J. Bols

H. J. Leese


Elevated plasma nonesterified fatty acid (NEFA) concentrations are associated with negative energy balance and metabolic disorders such as obesity and type II diabetes. Such increased plasma NEFA concentrations induce changes in the microenvironment 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 upregulated. From a functional perspective, inhibition of fatty acid 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.


Van Hoeck, V., Leroy, J. L. M. R., Arias Alvarez, M., Rizos, D., Gutierrez-Adan, A., Schnorbusch, K., …Sturmey, R. G. (2013). Oocyte developmental failure in response to elevated nonesterified fatty acid concentrations: mechanistic insights. Reproduction, 145(1), 33-44.

Journal Article Type Article
Acceptance Date Oct 23, 2012
Online Publication Date Oct 29, 2012
Publication Date Jan 8, 2013
Journal Reproduction
Print ISSN 1470-1626
Electronic ISSN 1741-7899
Publisher BioScientifica
Peer Reviewed Peer Reviewed
Volume 145
Issue 1
Pages 33-44
Keywords Obstetrics and Gynaecology; Cell Biology; Embryology; Endocrinology; Reproductive Medicine
Public URL