title: Differential gene expression profile in bovine blastocysts resulting from hyperglycemia exposure during early cleavage stages.
abstract: To understand the compromised survival of embryos derived from assisted reproductive techniques, transcriptome survey of early embryonic development has shown the impact of in vitro culture environment on gene expression in bovine or other living species. However, how the differentially expressed genes translate into developmentally compromised embryos is unresolved. We therefore aimed to characterize transcriptomic markers expressed by bovine blastocysts cultured in conditions that are known to impair embryo development. As increasing glucose concentrations has been shown to be stressful for early cleavage stages of mammalian embryos and to decrease subsequent blastocyst survival, in vitro-matured/fertilized bovine zygotes were cultured in control (0.2 mM) or high-glucose (5 mM) conditions until the 8- to 16-cell stage, and then transferred to control media until they reached the blastocyst stage. The concentration of 5 mM glucose was chosen as a stress treatment because there was a significant effect on blastocyst rate without the treatment's being lethal as with 10 mM. Microarray analysis revealed gene expression differences unrelated to embryo sex or hatching. Overrepresented processes among differentially expressed genes in treated blastocysts were extracellular matrix signalling, calcium signaling, and energy metabolism. On a pathophysiological level, higher glucose treatment impacts pathways associated with diabetes and tumorigenesis through genes controlling the Warburg effect, i.e., emphasis on use of anaerobic glycolysis rather than oxidative phosphorylation. These results allowed us to conclude that disruption of in vitro preattachment development is concomitant with gene expression modifications involved in metabolic control.
authors.affiliation: Département des Sciences Animales, Centre de Recherche en Biologie de la Reproduction, Université Laval, Québec, Canada.
authors.forename: Gaël L M
authors.initials: GL
authors.lastname: Cagnone
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dufort
authors.forename: Christian
authors.initials: C
authors.lastname: Vigneault
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Sirard
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D002970:Cleavage Stage, Ovum / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism*; D066298:In Vitro Techniques; D023421:Models, Animal
chemical_list: D005947:Glucose