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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, 2026
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)

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Scientific publications (4)
(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)
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., . (14/22887-0, 20/08478-0, 15/21829-9, 20/13075-2)
FERST, JULIANA GERMANO; CHAVES, MATHEUS ANDRADE; SILVA, AMANDA NESPOLO; SALDANHA, SCHAIENNI FONTOURA; FERREIRA, ROGERIO; NOCITI, RICARDO PERECIN; DOS SANTOS, ANGELICA CAMARGO; SOUZA, SAMUEL VOLPE; CHIARATTI, MARCOS ROBERTO; PUGLIESI, GUILHERME; et al. Uterine Extracellular Vesicles Can Emulate the Long-Term Effects of Post-Partum Negative Energy Balance in Dairy Cows. Molecular Reproduction and Development, v. 92, n. 10, p. 21-pg., . (22/01433-7, 22/01505-8, 14/22887-0, 23/04558-8, 15/21829-9, 21/06645-0, 20/13075-2)
LAZZARI, JESSICA; DE MORAES, FABIANE PEREIRA; VARGAS JUNIOR, SERGIO FARIAS; DE CASTRO, NATALIA AVILA; MAGGI, GABRIEL; VIEIRA, ARNALDO DINIZ; PEGORARO, LIGIA MARGARETH CANTARELLI; RODRIGUES, PEDRO HENRIQUE DE OLIVEIRA SWARTELE; FERST, JULIANA GERMANO; DA SILVEIRA, JULIANO COELHO; et al. Time-dependent intrafollicular cyclooxygenase (COX) inhibition with prostaglandin: Effects on bovine ovulation and follicular fluid extracellular vesicles miRNAs. Theriogenology, v. 253, p. 11-pg., . (20/13075-2, 21/06645-0, 15/21829-9, 14/22887-0)
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, . (20/08478-0, 15/21829-9, 20/13075-2, 14/22887-0)