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METABOLOEPYGENETICS: THE STUDY OF BOVINE EMBRYO DEVELOPMENT UNDER A NEW PERSPECTIVE

Grant number: 18/19909-2
Support Opportunities:Scholarships abroad - Research
Effective date (Start): March 20, 2019
Effective date (End): May 19, 2019
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Reproduction
Principal Investigator:Marcella Pecora Milazzotto
Grantee:Marcella Pecora Milazzotto
Host Investigator: Pablo Juan Ross
Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
Research place: University of California, Davis (UC Davis), United States  

Abstract

The effects of the in vitro system on the development of the pre-implantation embryo are determinant for its viability and post-transfer success. Modifications in this system have been suggested, especially in relation to the increase of energy metabolism by the modulation of substrates such as glucose, pyruvate and several amino acids. However, the impact of these supplements may be beyond the generation of ATP. During the first cleavages, the embryo mainly uses pyruvate and to some extent lactate, glutamine and aspartate to generate energy and has limited capacity to metabolize glucose. The energetic demand is increased by the activation of the embryonic genome, leading the embryo to metabolize glucose more efficiently, especially due to the greater activity of the glycolytic pathway. In this pathway, pyruvate is produced, converted to acetyl-CoA which is directed to the tricarboxylic acid cycle. Among other intermediates, the TCA cycle generates citrate which may, outside the mitochondria, be converted back to acetyl-CoA, providing precursors for lipid synthesis. It has also been shown that this same acetyl-CoA can deflect its route and serve as a precursor for the acetylation of histones, modifying the overall gene transcription pattern of the cell. Thus, the hypothesis of this present work is that the pharmacological modulation of the glycolytic pathway in bovine embryos produced in vitro can lead to different profiles of citrate and acetyl-CoA generation, interfering with the histone acetylation pattern, thus altering its metabolic profile And the potency of the blastocyst cells. To this end, the glycolytic pathway in the blastocyst will be pharmacologically modulated and the embryos will be evaluated by means of: glucose consumption capacity and pyruvate production; ATP levels, mitochondrial membrane potential and reactive oxygen species, the presence of PDK1, active ACL and HAT, the expression of genes related to the pathway studied, as well as the overall acetylation pattern of the embryos. These data are expected to contribute to the understanding of the role of the glycolytic pathway in the epigenetic pattern of bovine embryos produced in vitro.

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