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

• Grant number: 17/18384-0
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2018
• End date: September 30, 2020
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Marcella Pecora Milazzotto
• Grantee: Marcella Pecora Milazzotto
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated scholarship(s): 18/24756-0 - Metaboloepigenetics: the study of bovine embryos development under a new perspective, BP.TT; 18/09014-8 - Metaboloepygenetics: the study of the bovine embryo development under a new perspective, BP.TT

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. (AU)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS SANTOS, ERIKA CRISTINA; DA FONSECA JUNIOR, ALDCEJAM MARTINS; DE LIMA, CAMILA BRUNA; ISPADA, JESSICA; ALCANTARA DA SILVA, JOAO VITOR; MILAZZOTTO, MARCELLA PECORA. Less is more: Reduced nutrient concentration during in vitro culture improves embryo production rates and morphophysiology of bovine embryos. Theriogenology, v. 173, p. 37-47, OCT 1 2021. (17/18384-0, 16/00350-0)

ISPADA, JESSICA; DA FONSECA JUNIOR, ALDCEJAM MARTINS; RAMOS SANTOS, OTAVIO LUIZ; DE LIMA, CAMILA BRUNA; DOS SANTOS, ERIKA CRISTINA; DA SILVA, VINICIUS LOURENCO; ALMEIDA, FERNANDA NASCIMENTO; LEITE, SAUL DE CASTRO; ROSS, PABLO JUAN; MILAZZOTTO, MARCELLA PECORA. Metabolism-driven post-translational modifications of H3K9 in early bovine embryos. Reproduction, v. 162, n. 3, p. 181-191, SEP 2021. (17/18384-0, 18/11668-6, 15/03381-0)

DE LIMA, CAMILA BRUNA; DOS SANTOS, ERIKA CRISTINA; ISPADA, JESSICA; FONTES, PATRICIA KUBO; GOUVEIA NOGUEIRA, MARCELO FABIO; DIAS DOS SANTOS, CHARLES MORPHY; MILAZZOTTO, MARCELLA PECORA. The dynamics between in vitro culture and metabolism: embryonic adaptation to environmental changes. SCIENTIFIC REPORTS, v. 10, n. 1, SEP 24 2020. (12/50533-2, 17/18384-0, 15/03381-0, 17/11768-8)

MARCELLA PECORA MILAZZOTTO; CAMILA BRUNA DE LIMA; ALDCEJAM MARTINS DA FONSECA JUNIOR; ERIKA CRISTINA DOS SANTOS; JESSICA ISPADA. Erasing gametes to write blastocysts: metabolism as the new player in epigenetic reprogramming. Animal Reproduction, v. 17, n. 3, 2020-08-10. (17/18384-0)

ISPADA, JESSICA; DA FONSECA JUNIOR, ALDCEJAM MARTINS; DE LIMA, CAMILA BRUNA; DOS SANTOS, ERIKA CRISTINA; FONTES, PATRICIA KUBO; GOUVEIA NOGUEIRA, MARCELO FABIO; DA SILVA, VINICIUS LOURENCO; ALMEIDA, FERNANDA NASCIMENTO; LEITE, SAUL DE CASTRO; CHITWOOD, JAMES LEE; et al. Tricarboxylic Acid Cycle Metabolites as Mediators of DNA Methylation Reprogramming in Bovine Preimplantation Embryos. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 18, p. 16-pg., 2020-09-01. (12/50533-2, 18/11668-6, 17/18384-0, 15/03381-0)

MILAZZOTTO, MARCELLA PECORA; DE LIMA, CAMILA BRUNA; DA FONSECA JUNIOR, ALDCEJAM MARTINS; DOS SANTOS, ERIKA CRISTINA; ISPADA, JESSICA. Erasing gametes to write blastocysts: metabolism as the new player in epigenetic reprogramming. ANIMAL REPRODUCTION, v. 17, n. 3, p. 23-pg., 2020-01-01. (17/18384-0)

ANNES, KELLY; DE LIMA, CAMILA BRUNA; ISPADA, JESSICA; DOS SANTOS, ERIKA CRISTINA; FONTES, PATRICIA KUBO; NICHI, MARCILIO; GOUVEIA NOGUEIRA, MARCELO FABIO; SUDANO, MATEUS JOSE; MILAZZOTTO, MARCELLA PECORA. Insulin-like growth factor-1 (IGF-1) selectively modulates the metabolic and lipid profile of bovine embryos according to their kinetics of development. Theriogenology, v. 204, p. 7-pg., 2023-04-06. (17/18384-0, 16/05986-0)

DA FONSECA JUNIOR, ALDCEJAM MARTINS; GAITA, VINCENZO; ARGUMEDO, DANIEL RICARDO; DE CASTRO, LETICIA SIGNORI; DE AGOSTINI LOSANO, JOAO DIEGO; LEITE, ROBERTA FERREIRA; NICHI, MARCILIO; D'AVILA ASSUMPCAO, MAYRA ELENA ORTIZ; DE ARAUJO, DANIELE RIBEIRO; RANHA NEVES, ANTONIO ALVARO; et al. Changes in fertilization medium viscosity using hyaluronic acid impact bull sperm motility and acrosome status. REPRODUCTION IN DOMESTIC ANIMALS, v. 55, n. 8, p. 974-983, AUG 2020. (17/18384-0)