RT Journal Article T1 Oocyte developmental failure in response to elevated non-esterified fatty acid concentrations: mechanistic insights A1 Van Hoeck, Veerle A1 Leroy, J.L.M.R. A1 Arias Álvarez, María A1 Rizos, D. A1 Gutiérrez Adán, Alfonso A1 Schnorbusch, K. A1 Bols, Peter E.J. A1 Leese, H.J. A1 Sturmey, R.G. AB 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 b-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 b-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 fromNEFA-exposed maturing oocytes. PB Society for Reproduction and Fertility SN 1470-1626 YR 2013 FD 2013-01-30 LK https://hdl.handle.net/20.500.14352/102788 UL https://hdl.handle.net/20.500.14352/102788 LA eng DS Docta Complutense RD 22 abr 2025