Dairy cows metabolic status effects on epigenetic changes in the embryo and endometrium: the role of extracellular vesicles

• Grant number: 20/13075-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2021
• End date: September 30, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Juliano Coelho da Silveira
• Grantee: Juliana Germano Ferst
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated research grant: 21/06645-0 - Extracellular vesicles as a platform for diagnostic and manipulation of the in vitro embryo production system: the next generation in animal reproduction, AP.JP2
• Associated scholarship(s): 23/15072-9 - EFFECTS OF EXTRACELLULAR VESICLES FROM UTERINE ENVIRONMENT EXPOSED TO NEGATIVE ENERGY BALANCE ON EMBRYO METABOLISM IN CATTLE, BE.EP.PD

Abstract

Dairy cows milk production has increased over the past decade as a result of intense genetic selection. However, the advances in genetic selection of dairy herds did not come with an improvement of reproductive parameters. Negative Energy Balance (NEB) during postpartum period is important risk factor in the establishment of reproductive failure in high producing dairy cows and has significant economic impact due to the reduction in animal production. Metabolites generated during NEB state negatively affect reproductive cells. However, there is a gap in knowledge about intercellular communication in the follicular and uterine environment of cows affected by NEB. Extracellular Vesicles (EVs; exosomes and microvesicles) containing miRNAs and proteins are secreted by follicular and uterine cells. VEs are mediators of intercellular communication, modulate several reproductive processes and can carry molecular signals in response to stressors such as BEN. Epigenetic mechanisms are known to regulate critical cells functions and modulate cell adaptation responses including cell metabolism and stress. In this way, epigenetic changes due to exposure to a stressful environment may be one of the causes of the negative effects observed in reproductive cells exposed to NEB. The hypotheses that will be tested are: follicular fluid EVs isolated from cows presenting NEB can affect oocyte quality, early embryonic development and modulate epigenetic changes; uterine fluid EVs from cows with NEB modulate epigenetic and molecular changes in endometrial cells. To test these hypotheses, the follicular and uterine fluid from heifers and cows with high and low NEB state will be collected 30 and 60 day after calving and VEs will be isolated and analyzed. The EVs isolated will be added to the oocyte maturation and endometrial cell culture medium to evaluate the effects on the epigenetic and molecular modulations of these cells. The first aim is to investigate the functions of the vesicles present in the follicular fluid of dairy cows with different metabolic status during oocyte maturation and embryo development, evaluating specially the epigenetic changes. The second aim is to determine the content of the vesicles present in the uterine fluid of dairy cows with different metabolic status and to investigate the functions of these vesicles in the endometrial cells. The results obtained in this research will make possible to understand the follicular and uterine environment of cows in NEB state in two important moments for the IA allowing the development of new technologies and management methods to reduce the economic losses in milk production. (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)

NATÁLIA MARINS BASTOS; JULIANA GERMANO FERST; RODRIGO SILVA GOULART; JULIANO COELHO DA SILVEIRA. The role of the oviduct and extracellular vesicles during early embryo development in bovine. Animal Reproduction, v. 19, n. 1, 2022-04-20. (20/08478-0, 15/21829-9, 20/13075-2, 14/22887-0)

BASTOS, NATALIA MARINS; FERST, JULIANA GERMANO; GOULART, RODRIGO SILVA; DA SILVEIRA, JULIANO COELHO. The role of the oviduct and extracellular vesicles during early embryo development in bovine. ANIMAL REPRODUCTION, v. 19, n. 1, p. 13-pg., 2022-01-01. (14/22887-0, 20/08478-0, 15/21829-9, 20/13075-2)