Tricarboxylic Acid Cycle Metabolites as Mediators of DNA Methylation Reprogramming in Bovine Preimplantation Embryos.

Autor: Ispada J; Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo André, 09210-580 São Paulo, Brazil.; Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 São Paulo, Brazil., da Fonseca Junior AM; Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo André, 09210-580 São Paulo, Brazil., de Lima CB; Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo André, 09210-580 São Paulo, Brazil.; Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle (CRDSI), Département des Sciences Animales, Faculté des Sciences de l'Agriculture et de l'Alimentation, Université Laval, Québec, QC G1V 0A6, Canada., Dos Santos EC; Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo André, 09210-580 São Paulo, Brazil., Fontes PK; Laboratory of Phytomedicines, Pharmacology and Biotechnology, Department of Pharmacology, Institute of Biosciences, São Paulo State University (Unesp), Campus of Botucatu, 18618-689 São Paulo, Brazil., Nogueira MFG; Laboratory of Phytomedicines, Pharmacology and Biotechnology, Department of Pharmacology, Institute of Biosciences, São Paulo State University (Unesp), Campus of Botucatu, 18618-689 São Paulo, Brazil.; Department of Biological Sciences, School of Sciences and Languages, São Paulo State University (Unesp), Campus of Assis, 19806-900 São Paulo, Brazil., da Silva VL; Bioinformatics and Health Informatics Group, Center for Engineering, Modeling and Applied Social Sciences, Universidade Federal do ABC, São Bernardo do Campo, 09606-045 São Paulo, Brazil., Almeida FN; Bioinformatics and Health Informatics Group, Center for Engineering, Modeling and Applied Social Sciences, Universidade Federal do ABC, São Bernardo do Campo, 09606-045 São Paulo, Brazil., Leite SC; Center for Mathematics Computation and Cognition, Universidade Federal do ABC, Santo André, 09210-580 São Paulo, Brazil., Chitwood JL; Department of Animal Science, University of California Davis, Davis, CA 95616, USA., Ross PJ; Department of Animal Science, University of California Davis, Davis, CA 95616, USA., Milazzotto MP; Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo André, 09210-580 São Paulo, Brazil.; Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 São Paulo, Brazil.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 Sep 18; Vol. 21 (18). Date of Electronic Publication: 2020 Sep 18.
DOI: 10.3390/ijms21186868
Abstrakt: In many cell types, epigenetic changes are partially regulated by the availability of metabolites involved in the activity of chromatin-modifying enzymes. Even so, the association between metabolism and the typical epigenetic reprogramming that occurs during preimplantation embryo development remains poorly understood. In this work, we explore the link between energy metabolism, more specifically the tricarboxylic acid cycle (TCA), and epigenetic regulation in bovine preimplantation embryos. Using a morphokinetics model of embryonic development (fast- and slow-developing embryos), we show that DNA methylation (5mC) and hydroxymethylation (5hmC) are dynamically regulated and altered by the speed of the first cleavages. More specifically, slow-developing embryos fail to perform the typical reprogramming that is necessary to ensure the generation of blastocysts with higher ability to establish specific cell lineages. Transcriptome analysis revealed that such differences were mainly associated with enzymes involved in the TCA cycle rather than specific writers/erasers of DNA methylation marks. This relationship was later confirmed by disturbing the embryonic metabolism through changes in α-ketoglutarate or succinate availability in culture media. This was sufficient to interfere with the DNA methylation dynamics despite the fact that blastocyst rates and total cell number were not quite affected. These results provide the first evidence of a relationship between epigenetic reprogramming and energy metabolism in bovine embryos. Likewise, levels of metabolites in culture media may be crucial for precise epigenetic reprogramming, with possible further consequences in the molecular control and differentiation of cells.
Databáze: MEDLINE
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