Extracellular Vesicles Containing NPR2 and EGFr Supplemented During Oocyte Maturation: Effects on Transzonal Projection Communication, Meiotic Resumption, and Oocyte Quality

• Grant number: 24/03052-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2025
• End date: March 31, 2026
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Juliano Coelho da Silveira
• Grantee: Luca Angi Souza
• 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

Abstract

In cattle, an antral follicle requires approximately 40 days to develop into a pre-ovulatory follicle. However, when the follicle is aspirated and cumulus-oocyte complexes (COCs) are placed in in vitro maturation (IVM) media, nuclear maturation occurs in less than 24 hours, resulting in a desynchronization between nuclear and cytoplasmic maturation. Cytoplasmic immaturity leads to inadequate modulation of mRNA and protein reserves, which are crucial for early embryo development. Under physiological conditions, meiotic arrest is sustained by signaling from C-type natriuretic peptide (CNP), synthesized by mural granulosa cells, which binds to the NPR2 receptor. This mechanism allows the meiotic cell cycle to remain arrested, preserving oocyte components until ovulation. Unpublished results from our research group indicate the presence of NPR2 and EGFR receptors in follicular extracellular vesicles (EVs), allowing us to hypothesize that EVs could transfer these receptors to cumulus cells (CCs) and, thus, modulate meiotic arrest or resumption. This project aims to assess whether supplementation with EVs containing NPR2 and EGFR in NPPC-containing medium can maintain meiotic arrest; and, when in AREG-containing medium, induce a higher rate of resumption, thereby enhancing the synchronization of heterogeneous COC populations, as well as the synchronization of nuclear and cytoplasmic maturation, potentially improving oocyte competence. Demonstrating this mechanism and applying it in vitro may allow for more physiological oocyte maturation, producing oocytes with greater competence to yield more and better-quality blastocysts. These interventions are expected to optimize in vitro embryo production (IVP) in cattle and could serve as an experimental model for reproductive studies in humans. (AU)