title: Oocyte developmental failure in response to elevated nonesterified fatty acid concentrations: mechanistic insights.
abstract: 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 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.
authors.affiliation: Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, Faculty of Biomedical, Pharmaceutical and Veterinary Sciences, Gamete Research Center, University of Antwerp, Universiteitsplein 1-Gebouw U, B-2610 Wilrijk, Belgium. veerle.vanhoeck@ua.ac.be
authors.forename: V
authors.initials: V
authors.lastname: Van Hoeck
authors.forename: J L M R
authors.initials: JL
authors.lastname: Leroy
authors.forename: M
authors.initials: M
authors.lastname: Arias Alvarez
authors.forename: D
authors.initials: D
authors.lastname: Rizos
authors.forename: A
authors.initials: A
authors.lastname: Gutierrez-Adan
authors.forename: K
authors.initials: K
authors.lastname: Schnorbusch
authors.forename: P E J
authors.initials: PE
authors.lastname: Bols
authors.forename: H J
authors.initials: HJ
authors.lastname: Leese
authors.forename: R G
authors.initials: RG
authors.lastname: Sturmey
mesh_terms: D000818:Animals; D002417:Cattle / Q000196:embryology*; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000502:physiology; D059471:In Vitro Oocyte Maturation Techniques; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D023421:Models, Animal; D019301:Oleic Acid / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D019308:Palmitic Acid / Q000494:pharmacology; D013229:Stearic Acids / Q000494:pharmacology
chemical_list: D005230:Fatty Acids, Nonesterified; D013229:Stearic Acids; D019301:Oleic Acid; D019308:Palmitic Acid; C031183:stearic acid