Use of the ketone body beta-hydroxybutyric acid as an experimental tool to study the link among metabolism, epigenetic and reproduction in cattle

• Grant number: 16/13416-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): January 01, 2017
• Effective date (End): May 31, 2022
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Flávio Vieira Meirelles
• Grantee: Juliano Rodrigues Sangalli
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID
• Associated scholarship(s): 18/09552-0 - Epigenetic effect of the ketone body beta-hydroxybutyrate on histone beta-hydroxybutyrylation in bovine cumulus-oocyte complexes, BE.EP.PD

Abstract

In the past 20 years has been observed a decline in the fertility of dairy cows, whose etiology is complex. Several factors have been identified as the cause of reduced fertility, among them metabolic disorders such as negative energy balance (NEB). Cows in NEB increase serum concentrations of ketone bodies, and the ²-hydroxybutyric acid (BOHB) is the main ketone body circulating in cows. The high level of (BOHB) observed in the serum is paralleled with the levels in the follicular fluid, which might affect oocyte maturation and consequently the embryonic development. However, the mechanisms through the ketone body affect the animal reproduction are not fully understood at the molecular level. Recently, BOHB was demonstrated to be a potent endogenous inhibitor of histone deacetylases (HDACs). The HDACs are enzymes that remove the radical acetyl of histones, thus carry out broad regulatory functions in cells, mainly regulating gene expression. In this way, the inhibition of HDACs caused by BOHB exposure does affect the cellular through histone hyperacetylation. Since the levels of BOHB fluctuates depending on animal diet, this molecule act as a link connecting the animal nutrition with the cellular metabolism and regulation of gene expression. However, the mechanism by which the animal nutrition can affect its epigenome and consequently the reproduction is elusive. Based on this, this project aims to investigate how the exposure of cumulus-oocyte complexes (COCs) to the ketone body BOHB during the in vitro oocyte maturation alter the epigenome and the population of RNAs, and whether these changes affect oocyte maturation and in vitro embryo development. We hope with this project to understand the molecular mechanisms by which one ketone body commonly altered in dairy cows, the BOHB, might affect the reproductive performance of these animals. (AU)

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)

SANGALLI, JULIANO RODRIGUES; SAMPAIO, RAFAEL VILAR; DEL COLLADO, MAITE; DA SILVEIRA, JULIANO COELHO; CAMARA DE BEM, TIAGO HENRIQUE; PERECIN, FELIPE; SMITH, LAWRENCE CHARLES; MEIRELLES, FLAVIO VIEIRA. Metabolic gene expression and epigenetic effects of the ketone body beta-hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos (vol 8, 13766, 2018). SCIENTIFIC REPORTS, v. 8, p. 1-pg., 2018-11-16. (16/13416-9, 14/22887-0, 14/21034-3, 12/50533-2, 14/50947-7, 13/06673-7, 13/08135-2, 14/21097-5)

SANGALLI, JULIANO RODRIGUES; SAMPAIO, RAFAEL VILAR; DEL COLLADO, MAITE; DA SILVEIRA, JULIANO COELHO; CAMARA DE BEM, TIAGO HENRIQUE; PERECIN, FELIPE; SMITH, LAWRENCE CHARLES; MEIRELLES, FLAVIO VIEIRA. Metabolic gene expression and epigenetic effects of the ketone body beta-hydroxybutyrate. SCIENTIFIC REPORTS, v. 8, SEP 13 2018. (13/08135-2, 16/13416-9, 13/06673-7, 12/50533-2, 14/21097-5, 14/22887-0, 14/21034-3)