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Effect of introducing embryonic or somatic mitochondria on development and on mitochondrial inheritance in cattle

Abstract

Recent epidemiologic studies have confirmed that pathologies caused by mutations in the mitochondrial DNA (mtDNA) are a major cause of diseases in humans, affecting at least one in 4,000 people. Nonetheless, due to the unique inheritance pattern of these diseases, no method to prevent their transmission to the next generation is avaliable. Currently, only the nuclear transfer has the potential to be used to prevent it, with however many barriers to be overcome before it becomes available clinically. Recently, we developed a new methodology that enables to remove over than 60% of oocyte/zygote mitochondria. This has led to new perspectives concerning about the use of cytoplasmic transfer as a tool to prevent inheritance of mtDNA diseases. If a large amount of mitochondria was introduced into the depleted zygote, the mutant mtDNA would be diluted to a low level, potentially preventing transmission of many pathologies caused by the mtDNA. This project aims to investigate two methodologies to introduce a large amount of mitochondria into the depleted zygote n order to increase the contrubuition of introduced mtDNA in embryos and offspring. Therefore, this proposal will test the use of two sources of mitochondria from i) the cytoplasmic fraction rich in mitochondria obtained after zygote centrifugation (embryonic mitochondria) and ii) purified mitochondria from somatic cells (somatic mitochondria). It will be analyzed whether there is an effect of mitochondrial source on development to term as well as the heteroplasmy in offspring. In case of we find a decrease of heteroplasmy during development other studies will be carried out to address the reasons of such effect. (AU)

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Scientific publications (5)
(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)
PESSOA, L. V. F.; BRESSAN, F. F.; CHIARATTI, M. R.; PIRES, P. R. L.; PERECIN, F.; SMITH, L. C.; MEIRELLES, F. V.. Mitochondrial DNA dynamics during in vitro culture and pluripotency induction of a bovine Rho0 cell line. Genetics and Molecular Research, v. 14, n. 4, p. 14093-14104, . (13/08135-2, 11/08376-4, 10/13384-3)
FERREIRA, ROBERTA MACHADO; CHIARATTI, MARCOS ROBERTO; MACABELLI, CAROLINA HABERMANN; RODRIGUES, CARLOS ALBERTO; FERRAZ, MARCIO LEAO; WATANABE, YEDA FUMIE; SMITH, LAWRENCE CHARLES; MEIRELLES, FLAVIO VIEIRA; BARUSELLI, PIETRO SAMPAIO. The Infertility of Repeat-Breeder Cows During Summer Is Associated with Decreased Mitochondrial DNA and Increased Expression of Mitochondrial and Apoptotic Genes in Oocytes. BIOLOGY OF REPRODUCTION, v. 94, n. 3, . (09/00938-3, 10/13384-3, 11/14207-0, 10/09561-7, 12/07510-1)
MACHADO, THIAGO SIMOES; MACABELLI, CAROLINA HABERMANN; SANGALLI, JULIANO RODRIGUES; RODRIGUES, THIAGO BITTENCOURT; SMITH, LAWRENCE CHARLES; MEIRELLES, FLAVIO VIEIRA; CHIARATTI, MARCOS ROBERTO. Real-Time PCR Quantification of Heteroplasmy in a Mouse Model with Mitochondrial DNA of C57BL/6 and NZB/BINJ Strains. PLoS One, v. 10, n. 8, . (12/50231-6, 10/13384-3, 10/09561-7, 12/12951-7)
MACABELLI, CAROLINA HABERMANN; FERREIRA, ROBERTA MACHADO; GIMENES, LINDSAY UNNO; TONIZZA DE CARVALHO, NELCIO ANTONIO; SOARES, JULIA GLEYCI; AYRES, HENDERSON; FERRAZ, MARCIO LEAO; WATANABE, YEDA FUMIE; WATANABE, OSNIR YOSHIME; SANGALLI, JULIANO RODRIGUES; et al. Reference Gene Selection for Gene Expression Analysis of Oocytes Collected from Dairy Cattle and Buffaloes during Winter and Summer. PLoS One, v. 9, n. 3, . (09/00938-3, 10/13384-3, 11/14207-0, 10/09561-7, 12/07510-1)
SANGALLI, JULIANO RODRIGUES; CHIARATTI, MARCOS ROBERTO; CAMARA DE BEM, TIAGO HENRIQUE; DE ARAUJO, RENO ROLDI; BRESSAN, FABIANA FERNANDES; SAMPAIO, RAFAEL VILAR; PERECIN, FELIPE; SMITH, LAWRENCE CHARLES; KING, WILLIAN ALLAN; MEIRELLES, FLAVIO VIEIRA. Development to Term of Cloned Cattle Derived from Donor Cells Treated with Valproic Acid. PLoS One, v. 9, n. 6, . (13/06673-7, 10/19768-8, 10/13384-3)

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