Fertility effect of the knockout of Mitofusin 1 on murine oocytes

• Grant number: 16/11942-5
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): September 01, 2016
• Effective date (End): August 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Marcos Roberto Chiaratti
• Grantee: Karen Freire Carvalho
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 17/16234-1 - Effects of the overexpression of mitofusin 1 and mitofusin 2 in oocytes during in vitro folliculogenesis, BE.EP.MS

Abstract

It is known that mitochondria play a fundamental role when it comes to oocyte fertility. Several studies have associated infertility in women over 40 years old with mitochondrial defects, thus, mitochondria have been an important therapy target in assisted reproduction techniques. However, the molecular mechanisms that drive these mitochondrial defects are unknown. In this context, the huge amount of mtDNA in oocytes, the greatest when compared with other cell types, is highlighted, along with the rounded and small format of oocyte's mitochondria, which contrasts with the elongated morphology and typical tubular mitochondria in other cell types. Such characteristics are closely associated with mitochondrial fusion and fission events, which are crucial for mitochondrial proper function and mtDNA stability. Mitochondrial dynamics is coordinated, among other factors, by GTPases that promote membrane fusion (Mfn1, Mfn2 e Opa1) or fission (Dnm1l). It has been recently discovered that Mfn1 and Dnm1l, but not Mfn2, are essential for oocyte's competence, because Mfn1 or Dnm1l knockout affects follicle development, leading to oocyte development blockage and ovulation failure. Once Dnm1l is associated with other organelles, its effect over oocytes is huge and involves a multiorganelar rearrangement. Moreover, Mfn1 is present exclusively in mitochondria and still, its oocyte knockout leads to severe effect on mitochondrial function. However, the mechanism by which the absence of Mfn1 affects mitochondria, oocytes and follicle development is still unknown. Thereby, this work's goal is to study the role of Mfn1 in determining oocyte fertility. It is hoped that with this study we can shine a light on mitochondrial function regarding the oocyte competence process, which implicates in the development of new technologies for infertility treatment both in women and animals. (AU)

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)

CHIARATTI, MARCOS ROBERTO; GARCIA, BRUNA MARTINS; CARVALHO, KAREN FREIRE; MACHADO, THIAGO SIMOES; DA SILVA RIBEIRO, FERNANDA KARINA; MACABELLI, CAROLINA HABERMANN. The role of mitochondria in the female germline: Implications to fertility and inheritance of mitochondrial diseases. Cell Biology International, v. 42, n. 6, SI, p. 711-724, JUN 2018. (12/50231-6, 16/11935-9, 17/05899-2, 16/11942-5, 16/07868-4)

CHIARATTI, MARCOS R.; GARCIA, BRUNA M.; CARVALHO, KAREN F.; MACABELLI, CAROLINA H.; DA SILVA RIBEIRO, FERNANDA KARINA; ZANGIROLAMO, AMANDA F.; SARAPIAO, FABIANA D.; SENEDA, MARCELO M.; MEIRELLES, FLAVIO V.; GUIMARAES, FRANCISCO E. G.; et al. Oocyte mitochondria: role on fertility and disease transmission. ANIMAL REPRODUCTION, v. 15, n. 3, p. 231-238, JUL-SEP 2018. (16/07868-4, 17/05899-2, 12/50231-6, 16/11942-5, 16/11935-9)

CARVALHO, KAREN F.; MACHADO, THIAGO S.; GARCIA, BRUNA M.; ZANGIROLAMO, AMANDA F.; MACABELLI, CAROLINA H.; SUGIYAMA, FABRICIA H. C.; GREJO, MATEUS P.; NETO, J. DJACI AUGUSTO; TOSTES, KATIANE; RIBEIRO, FERNANDA K. S.; et al. Mitofusin 1 is required for oocyte growth and communication with follicular somatic cells. FASEB JOURNAL, v. 34, n. 6, APR 2020. (12/50231-6, 16/11935-9, 09/54035-4, 13/08135-2, 17/04372-0, 16/11942-5, 16/07868-4)

CHIARATTI, MARCOS ROBERTO; GARCIA, BRUNA MARTINS; CARVALHO, KAREN FREIRE; MACHADO, THIAGO SIMOES; DA SILVA RIBEIRO, FERNANDA KARINA; MACABELLI, CAROLINA HABERMANN. The role of mitochondria in the female germline: Implications to fertility and inheritance of mitochondrial diseases. Cell Biology International, v. 42, n. 6, p. 14-pg., 2018-06-01. (17/05899-2, 16/11935-9, 16/07868-4, 16/11942-5, 12/50231-6)

GARCIA, BRUNA M.; MACHADO, THIAGO S.; CARVALHO, KAREN F.; NOLASCO, PATRICIA; NOCITI, RICARDO P.; DEL COLLADO, MAITE; CAPO BIANCO, MARIA J. D.; GREJO, MATEUS P.; AUGUSTO NETO, JOSE DJACI; SUGIYAMA, FABRICIA H. C.; et al. Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis. MOLECULAR HUMAN REPRODUCTION, v. 26, n. 12, p. 938-952, DEC 2020. (10/51906-1, 17/05899-2, 17/04372-0, 18/20028-0, 18/06119-3, 16/11935-9, 09/54035-4, 12/50231-6, 16/11942-5)