Study of nitric oxide signaling in the mitochondrial metabolism of bovine oviduct cells

• Grant number: 20/09051-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2020
• End date: September 30, 2022
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Marcella Pecora Milazzotto
• Grantee: Heloise Cale da Rocha
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The oviduct is the anatomical region where life begins in most mammal species, as it is the meeting point between sperm and oocytes for fertilization, in addition to providing the appropriate environment for early embryonic development. The reproductive events that occur in the oviduct depend on synchronized signaling processes, which involve communication between the different types of cells involved. Nitric oxide (NO) is a short-lived free radical synthesized by NO-synthases (NOS), responsible for the conversion of L-Arginine to L-citrulline and NO. Both NOS and NO have been detected in different reproductive tissues, including embryos and oviduct cells. Despite this, the mechanisms of action of NO and its possible role in molecular and physiological control in these cells still need to be clarified. NO can have a variety of effects on cell type and environmentally dependent mitochondria that can affect energy production. Among them, the stimulation of mitochondrial biogenesis and, on the contrary, the inhibition of oxidative phosphorylation, both directly by inhibiting cytochrome c oxidase, and indirectly by blocking the tricarboxylic acid (TCA) cycle. The metabolites of mitochondrial energy production cycles have been described as essential for establishing molecular control, especially by epigenetic mechanisms, such as histone acetylation. Thus, given its presence in the oviduct and its impact on mitochondrial functioning, the hypothesis of this study is that differences in the availability of NO for bovine oviduct epithelial cells lead to changes in mitochondrial metabolism, with an impact on the histone acetylation profile. To verify this hypothesis, cells from the bovine oviduct epithelium will be cultured in vitro with different concentrations of nanoparticles associated with NO donors. In this model, mitochondrial activity, generation of reactive oxygen species and the expression pattern of ACO2, PGC-1alpha and SIRT1 and the levels of acetylation of lysine 9 from histone 3 of the cells will be evaluated. This is expected to contribute to the understanding of the role of NO in the oviduct during the reproductive cycle.