Metaboloepigenetics: Interrelationships between energetic metabolism and DNA methylation in bovine embryos

• Grant number: 18/11668-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2019
• End date: October 03, 2022
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Marcella Pecora Milazzotto
• Grantee: Jéssica Ispada
• 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): 19/25094-4 - Metaboloepigenetics: interrelationships between energy metabolism and DNA methylation in bovine embryos, BE.EP.PD

Abstract

The in vitro culture system of embryos is crucial to determine its ability to reach the blastocyst stage and, in particular, its viability and success after transfer. Changes in this system are often employed and many of them are based in the addition of carbohydrates and amino acids as supplements of culture medium. However, this supplementation is usually in different concentrations than those observed physiologically, including for commercial embryos production. However, the impact of these supplements has not been fully elucidated and might have an effect beyond energy generation. One of the currently hypotheses in literature is that metabolites generated during energy production exerts direct and indirect control in methylation and demethylation status of cells, critical processes in pre-implantation embryonic development. During embryonic first cleavages occurs the DNA demethylation (actively and passively), which will be responsible for the production of totipotent cells, until 8-16 cells stage. Then, the DNA of these embryos must be re-methylated until, in the blastocyst stage, its blastomeres are classified as pluripotent and differentiated as belonging to inner cell mass or trophectoderm. It is known that the enzymes responsible for DNA demethylation use ±-ketoglutarate, a TCA cycle metabolite, for its activity. Therefore, the hypothesis of this work is that TCA cycle metabolites affect the DNA demethylation and methylation wave in bovine embryos. To confirm this hypothesis, TCA cycle metabolites will be modulated and their effects evaluated in DNA methylation parameters and gene transcription. It is expected that these results are going to contribute to understand the mechanisms that control embryonic DNA demethylation process and the role of metabolism in this event.

Scientific publications

(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)

ISPADA, JESSICA; MILAZZOTTO, MARCELLA PECORA. ilencing mark H3K27me3 is differently reprogrammed in bovine embryos with distinct kinetics of developmen. REPRODUCTION IN DOMESTIC ANIMALS, v. 57, n. 3, DEC 2021. (18/11668-6, 15/03381-0, 19/25982-7)

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)

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)