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Cell-secreted vesicles containing miRNAs modulate epigenetic changes during in vitro culture of bovine gametes and embryos

Grant number: 14/22887-0
Support type:Research Grants - Young Investigators Grants
Duration: September 01, 2015 - August 31, 2020
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:Juliano Coelho da Silveira
Grantee:Juliano Coelho da Silveira
Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
Assoc. researchers:Felipe Perecin ; Flávio Vieira Meirelles ; Luciano Andrade Silva
Associated grant(s):19/06696-3 - International consortium for the study of serum extracellular vesicles during early embryonic development of livestock animals, AP.R
18/04731-3 - Validation of miRNAs targets through luciferase assay in bovine granulosa cells, AV.EXT
15/21829-9 - Multi-user equipment approved in grant 2014/22887-0: Nanosight LM10, AP.EMU
Associated scholarship(s):19/04981-2 - Effects of extracellular vesicle supplementation during bovine embryo cleavage, BP.MS
17/19681-9 - Extracellular vesicles secreted by in vivo and in vitro produced bovine embryos: miRNA content and molecular effects on endometrium and corpus luteum, BP.DR
17/24326-3 - New method to evaluate intercellular communication mediated by extracellular vesicles within the bovine ovarian follicle, BP.IC
+ associated scholarships 18/01431-9 - PI3K-Akt signaling pathway effect in oocyte maturation and early embryo development in cattle, BP.PD
17/02037-0 - Description of a new mechanism involved in cellular communication between female reproductive system cells and oocyte mediated by extracellular vesicles and their impacts on oocyte maturation, fertilization and bovine embryo cleavage, BP.MS
15/17897-9 - Exosomal communication in the stem cells transdifferentiation in co-culture with neuronal cells, BP.DD
15/21674-5 - Dynamics of RNA expression and epigenetic changes during bovine oocyte maturation and embryonic development: comparing in vivo and in vitro systems, BP.IC
15/16985-1 - Cell-secreted vesicles containing miRNAs modulate epigenetic changes during in vitro culture of bovine gametes and embryos, BP.JP - associated scholarships

Abstract

The use of assisted reproduction techniques presents an alternative to solve reproductive problems in domestic species and humans. However, there is concern that epigenetic changes occurring during in vitro culture adversely affect tissue programing during fetal development and could lead to a higher pre-disposition to develop heart diseases, reproductive problems, and development of tumors, in adulthood. Epigenetic changes are regulated by DNA methylation, posttranscriptional histone modifications or microRNAs. MicroRNAs are non-coding RNA molecules that regulates gene expression during different tissue developing processes. Recently, cell-secreted vesicles called exosomes and microvesicles carrying bioactive materials including miRNAs were identified in different body fluids. Cell-secreted vesicles are considered a new class of intercellular communication with possible implications in different physiological processes. However, its role during oocyte maturation and embryo development is not well understood. Our main hypothesis that will be tested is that cell-secreted vesicles containing miRNAs originating from the reproductive tract modulate epigenetic changes during in vitro culture of gametes and embryos. In order to test this hypothesis cell-secreted vesicles will be isolated from follicular fluid and oviductual cells culture media and added to the oocyte maturation and embryo culture media. The first aim of this project is to determine the relationship between miRNAs and epigenetic changes during oocyte maturation and embryo development in vitro. The second aim of this project is to determine the effects exerted by vesicles secreted by reproductive tract cells on oocyte maturation rates, fertilization and embryo cleavage. The third aim of this proposal is to determine the role of cell-secreted vesicles and miRNAs in oocyte maturation and production of bovine embryos in high and low oxygen tension. Results obtained in this research will establish the role of cell-secreted vesicles by the reproductive tract in regulating epigenetic changes acquired during in vitro culture of oocytes and embryos, generating new therapeutic tools for domestic agriculture species and humans. (AU)

Scientific publications (17)
(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)
SANTOS ROBALLO, KELLY CRISTINE; DA SILVEIRA, JULIANO COELHO; BRESSAN, FABIANA FERNANDES; DE SOUZA, ALINE FERNANDA; PEREIRA, VITORIA MATTOS; PINZON PORRAS, JORGE ELIECER; ROS, FELIPE AUGUSTO; PULZ, LIDIA HILDEBRAND; STREFEZZI, RICARDO DE FRANCISCO; MARTINS, DANIELE DOS SANTOS; MEIRELLES, FLAVIO VIEIRA; AMBROSIO, CARLOS EDUARDO. Neurons-derived extracellular vesicles promote neural differentiation of ADSCs: a model to prevent peripheral nerve degeneration. SCIENTIFIC REPORTS, v. 9, AUG 1 2019. Web of Science Citations: 0.
ANDRADE, GABRIELLA MAMEDE; BOMFIM, MONALISA MEDRADO; DEL COLLADO, MAITE; MEIRELLES, FLAVIO VIEIRA; PERECIN, FELIPE; DA SILVEIRA, JULIANO COELHO. Oxygen tension modulates extracellular vesicles and its miRNA contents in bovine embryo culture medium. Molecular Reproduction and Development, v. 86, n. 8, p. 1067-1080, AUG 2019. Web of Science Citations: 0.
ANDRADE, GABRIELLA MAMEDE; DEL COLLADO, MAITE; MEIRELLES, FLAVIO VIEIRA; DA SILVEIRA, JULIANO COELHO; PERECIN, FELIPE. Intrafollicular barriers and cellular interactions during ovarian follicle development. ANIMAL REPRODUCTION, v. 16, n. 3, p. 485-496, JUL-SEP 2019. Web of Science Citations: 0.
CAVALCANTE MENDES DE AVILA, ANA CLARA FAQUINELI; ANDRADE, GABRIELLA MAMEDE; BRIDI, ALESSANDRA; GIMENES, LINDSAY UNNO; MEIRELLES, FLAVIO VIEIRA; PERECIN, FELIPE; DA SILVEIRA, JULIANO COELHO. Extracellular vesicles and its advances in female reproduction. ANIMAL REPRODUCTION, v. 16, n. 1, p. 31-38, JAN-MAR 2019. Web of Science Citations: 1.
DE FIGUEIREDO PESSOA, LAIS VICARI; LISBOA PIRES, PEDRO RATTO; DEL COLLADO, MAITE; GODOY PIERI, NAIRA CAROLINE; RECCHIA, KAIANA; SOUZA, ALINE FERNANDA; PERECIN, FELIPE; DA SILVEIRA, JULIANO COELHO; CESAR DE ANDRADE, ANDRE FURUGEN; AMBROSIO, CARLOS EDUARDO; BRESSAN, FABIANA FERNANDES; MEIRELLES, FLAVIO VIEIRA. Generation and miRNA Characterization of Equine Induced Pluripotent Stem Cells Derived from Fetal and Adult Multipotent Tissues. STEM CELLS INTERNATIONAL, 2019. Web of Science Citations: 1.
OTAGUIRI, KATIA KAORI; DOS SANTOS, DAIANE FERNANDA; SLAVOV, SVETOSLAV NANEV; DEPIERI, LIVIA VIEIRA; BONINI PALMA, PATRICIA VIANNA; MEIRELLES, FLAVIO VIEIRA; COVAS, DIMAS TADEU; DA SILVEIRA, JULIANO COELHO; KASHIMA, SIMONE. TAX-mRNA-Carrying Exosomes from Human T Cell Lymphotropic Virus Type 1-Infected Cells Can Induce Interferon-Gamma Production In Vitro. AIDS Research and Human Retroviruses, v. 34, n. 12 NOV 2018. Web of Science Citations: 1.
SANTOS, G.; BOTTINO, M. P.; SANTOS, A. P. C.; SIMOES, L. M. S.; SOUZA, J. C.; FERREIRA, M. B. D.; DA SILVEIRA, J. C.; AVILA, A. C. F. C. M.; BRIDE, A.; SALES, J. N. S. Subclinical mastitis interferes with ovulation, oocyte and granulosa cell quality in dairy cows. Theriogenology, v. 119, p. 214-219, OCT 1 2018. Web of Science Citations: 0.
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. Web of Science Citations: 2.
DEL COLLADO, MAITE; ANDRADE, GABRIELLA MAMEDE; MEIRELLES, FLAVIO VIEIRA; DA SILVEIRA, JULIANO COELHO; PERECIN, FELIPE. Contributions from the ovarian follicular environment to oocyte function. ANIMAL REPRODUCTION, v. 15, n. 3, p. 261-270, JUL-SEP 2018. Web of Science Citations: 1.
DA SILVEIRA, JULIANO C.; DE AVILA, ANA CLARA F. C. M.; GARRETT, HANNAH L.; BRUEMMER, JASON E.; WINGER, QUINTON A.; BOUMA, GERRIT J. Cell-secreted vesicles containing microRNAs as regulators of gamete maturation. Journal of Endocrinology, v. 236, n. 1, p. R15-R27, JAN 2018. Web of Science Citations: 13.
ANDRADE, G. M.; MEIRELLES, F. V.; PERECIN, F.; DA SILVEIRA, J. C. Cellular and extracellular vesicular origins of miRNAs within the bovine ovarian follicle. REPRODUCTION IN DOMESTIC ANIMALS, v. 52, n. 6, p. 1036-1045, DEC 2017. Web of Science Citations: 8.
BOMFIM, MONALISA M.; ANDRADE, GABRIELLA M.; DEL COLLADO, MAITE; SANGALLI, JULIANO R.; FONTES, PATRICIA K.; NOGUEIRA, MARCELO F. G.; MEIRELLES, FLAVIO V.; DA SILVEIRA, JULIANO C.; PERECIN, FELIPE. Antioxidant responses and deregulation of epigenetic writers and erasers link oxidative stress and DNA methylation in bovine blastocysts. Molecular Reproduction and Development, v. 84, n. 12, p. 1296-1305, DEC 2017. Web of Science Citations: 5.
DEL COLLADO, MAITE; DA SILVEIRA, JULIANO C.; OLIVEIRA, MARCELO L. F.; ALVES, BARBARA M. S. M.; SIMAS, ROSINEIDE C.; GODOY, ADRIANA T.; COELHO, MIRELA B.; MARQUES, LYGIA A.; CARRIERO, MATEUS M.; NOGUEIRA, MARCELO F. G.; EBERLIN, MARCOS N.; SILVA, LUCIANO A.; MEIRELLES, FLAVIO V.; PERECIN, FELIPE. In vitro maturation impacts cumulus-oocyte complex metabolism and stress in cattle. Reproduction, v. 154, n. 6, p. 881-893, DEC 2017. Web of Science Citations: 3.
DE BEM, T. H. C.; DA SILVEIRA, J. C.; SAMPAIO, R. V.; SANGALLI, J. R.; OLIVEIRA, M. L. F.; FERREIRA, R. M.; SILVA, L. A.; PERECIN, F.; KING, W. A.; MEIRELLES, F. V.; RAMOS, E. S. Low levels of exosomal-miRNAs in maternal blood are associated with early pregnancy loss in cloned cattle. SCIENTIFIC REPORTS, v. 7, OCT 30 2017. Web of Science Citations: 3.
ANDRADE, GABRIELLA MAMEDE; DA SILVEIRA, JULIANO COELHO; PERRINI, CLAUDIA; DEL COLLADO, MAITE; GEBREMEDHN, SAMUEL; TESFAYE, DAWIT; MEIRELLES, FLAVIO VIEIRA; PERECIN, FELIPE. The role of the PI3K-Akt signaling pathway in the developmental competence of bovine oocytes. PLoS One, v. 12, n. 9 SEP 18 2017. Web of Science Citations: 10.
DA SILVEIRA, JULIANO C.; ANDRADE, GABRIELLA M.; DEL COLLADO, MAITE; SAMPAIO, RAFAEL V.; SANGALLI, JULIANO R.; SILVA, LUCIANO A.; PINAFFI, FABIO V. L.; JARDIM, IZABELLE B.; CESAR, MARCELO C.; NOGUEIRA, MARCELO F. G.; CESAR, ALINE S. M.; COUTINHO, LUIZ L.; PEREIRA, RINALDO W.; PERECIN, FELIPE; MEIRELLES, FLAVIO V. Supplementation with small-extracellular vesicles from ovarian follicular fluid during in vitro production modulates bovine embryo development. PLoS One, v. 12, n. 6 JUN 15 2017. Web of Science Citations: 11.
DEL COLLADO, MAITE; DA SILVEIRA, JULIANO COELHO; SANGALLI, JULIANO RODRIGUES; ANDRADE, GABRIELLA MAMEDE; DA SILVA SOUSA, LETICIA RABELLO; SILVA, LUCIANO ANDRADE; MEIRELLES, FLAVIO VIEIRA; PERECIN, FELIPE. Fatty Acid Binding Protein 3 And Transzonal Projections Are Involved In Lipid Accumulation During In Vitro Maturation Of Bovine Oocytes. SCIENTIFIC REPORTS, v. 7, JUN 1 2017. Web of Science Citations: 13.

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