Author(s): Ispada, Jessica ; da Fonseca Junior, Aldcejam Martins ; de Lima, Camila Bruna ; Dos Santos, Erika Cristina ; Fontes, Patricia Kubo [UNESP] ; Nogueira, Marcelo Fábio Gouveia [UNESP] ; da Silva, Vinicius Lourenço ; Almeida, Fernanda Nascimento ; Leite, Saul de Castro ; Chitwood, James Lee ; Ross, Pablo Juan ; Milazzotto, Marcella Pecora
Date: 2021
Persistent ID: http://hdl.handle.net/11449/206516
Origin: Oasisbr
Subject(s): Bovine; DNA methylation; Embryo; Epigenetic; Metabolism
Made available in DSpace on 2021-06-25T10:33:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-02
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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.
Laboratory of Embryonic Metabolism and Epigenetics Center of Natural and Human Sciences Federal University of ABC
Institute of Biomedical Sciences University of Sao Paulo
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
Laboratory of Phytomedicines Pharmacology and Biotechnology Department of Pharmacology Institute of Biosciences São Paulo State University (Unesp), Campus of Botucatu
Department of Biological Sciences School of Sciences and Languages São Paulo State University (Unesp), Campus of Assis
Bioinformatics and Health Informatics Group Center for Engineering Modeling and Applied Social Sciences Universidade Federal do ABC
Center for Mathematics Computation and Cognition Universidade Federal do ABC
Department of Animal Science University of California Davis
Laboratory of Phytomedicines Pharmacology and Biotechnology Department of Pharmacology Institute of Biosciences São Paulo State University (Unesp), Campus of Botucatu
Department of Biological Sciences School of Sciences and Languages São Paulo State University (Unesp), Campus of Assis
FAPESP: 2012/50533-2
FAPESP: 2015/03381-0
FAPESP: 2017/18384-0
FAPESP: 2018/11668-6
